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12
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VCV
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12
12
RCV
stringlengths
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12
VariationID
int64
4
3.9M
HGVS_VariantDescription
stringlengths
33
112
GRCh38_Chr
stringclasses
24 values
GRCh38_Start
float64
14.8k
249M
GRCh38_Stop
float64
14.8k
249M
GRCh38_ReferenceAllele
stringclasses
16 values
GRCh38_AlternateAllele
stringclasses
167 values
VariantClassification
stringclasses
64 values
SubmissionClassification
stringclasses
17 values
Submitter
stringlengths
4
241
Gene
stringlengths
1
21
Comment
stringlengths
35
43.4k
DateLastEvaluated
stringdate
1965-01-01 00:00:00
2025-05-29 00:00:00
SubmissionDateLastEvaluated
stringdate
1965-01-01 00:00:00
2025-05-28 00:00:00
SubmissionReviewStatus
stringclasses
5 values
VariantAssertion
stringclasses
5 values
gene
stringlengths
2
15
aapos
int64
1
36k
aaref
stringclasses
21 values
aaalt
stringclasses
23 values
evidence_type
stringclasses
3 values
final_label
stringclasses
5 values
has_evidence
bool
2 classes
evidence_confidence
float32
0
1
predicted_evidence
stringclasses
4 values
P_Score
float32
0
1
B_Score
float32
0
1
sentence_index
int64
0
275
sentence
stringlengths
0
2.79k
stage1_score
float32
0
1
stage1_label
stringclasses
2 values
stage2_benign_score
float32
0
1
stage2_pathogenic_score
float32
0
1
predicted_evidence_sentence
stringclasses
5 values
SCV000020230
VCV000000069
RCV000000087
69
NM_000374.5(UROD):c.874C>G (p.Arg292Gly)
1
45,014,835
45,014,835
C
G
Pathogenic
pathogenic
OMIM
UROD
In 2 Dutch sisters with hepatoerythropoietic porphyria (HEP; see 176100), de Verneuil et al. (1992) demonstrated compound heterozygosity for a deletion inherited from the father and an R292G mutation inherited from the mother.
1992-07-01
1992-07-01
no assertion criteria provided
variation to disease
UROD
292
R
G
functional
null
false
0.0463
null
0
0
0
In 2 Dutch sisters with hepatoerythropoietic porphyria (HEP; see 176100), de Verneuil et al.
0.0282
no_evidence
0
0
None
SCV000020230
VCV000000069
RCV000000087
69
NM_000374.5(UROD):c.874C>G (p.Arg292Gly)
1
45,014,835
45,014,835
C
G
Pathogenic
pathogenic
OMIM
UROD
In 2 Dutch sisters with hepatoerythropoietic porphyria (HEP; see 176100), de Verneuil et al. (1992) demonstrated compound heterozygosity for a deletion inherited from the father and an R292G mutation inherited from the mother.
1992-07-01
1992-07-01
no assertion criteria provided
variation to disease
UROD
292
R
G
functional
null
false
0.0463
null
0
0
1
(1992) demonstrated compound heterozygosity for a deletion inherited from the father and an R292G mutation inherited from the mother.
0.0463
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
0
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
0.0207
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
1
Thus, the mutation originally designated TRP550CYS is now designated TRP1313CYS (W1313C).
0.0385
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
2
In the patient identified as case 7 in the report by Kyrle et al.
0.0824
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
3
(1988) with laboratory findings consistent with the diagnosis of type 2B von Willebrand disease (see 613554), Ware et al.
0.1913
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
4
The mutation is located in the domain of the molecule comprising residues 449 to 728 involved in the binding to platelet glycoprotein Ib-IX receptor complex (see 606672).
0.0279
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
5
This interaction is physiologically regulated so that it does not occur between circulating VWF and platelets but, rather, only at a site of vascular injury.
0.0194
no_evidence
0
0
None
SCV000020455
VCV000000287
RCV000000311
287
NM_000552.5(VWF):c.3939G>C (p.Trp1313Cys)
12
6,019,479
6,019,479
C
G
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,313
W
C
functional
null
false
0.1913
null
0
0
6
The abnormal VWF found in type 2B von Willebrand disease has a characteristically increased affinity for GP Ib and binds to the circulating platelets.
0.0913
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
0
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
0.0207
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
1
Thus, the mutation originally designated PHE751CYS is now designated PHE1514CYS (F1514C).
0.0335
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
2
In 8 patients from a large type 2A (see 613554) von Willebrand disease family, Gaucher et al.
0.0162
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
3
(1993) found a heterozygous T-to-G transversion resulting in a phe751-to-cys (F751C) substitution in the mature subunit.
0.0452
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
4
Type 2A is a variant form of von Willebrand disease characterized by the absence of high molecular weight VWF multimers in plasma.
0.035
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
5
(1993) noted that most of the candidate missense mutations potentially responsible for type 2A VWD have been found clustered within a short segment of VWF, lying between gly742 and glu875 of the mature subunit.
0.0153
no_evidence
0
0
None
SCV000020475
VCV000000304
RCV000000331
304
NM_000552.5(VWF):c.4541T>G (p.Phe1514Cys)
12
6,018,877
6,018,877
A
C
Pathogenic
pathogenic
OMIM
VWF
Goodeve (2010) noted that mutations in the VWF gene, which were sometimes numbered from the transcription start site of the mature protein, are now 'numbered from the first A of the ATG initiator methionine codon (A = +1) at the start of every protein (Met = +1), with cDNA rather than genomic DNA being commonly used as...
2010-05-01
2010-05-01
no assertion criteria provided
variation to disease
VWF
1,514
F
C
functional
null
false
0.6494
null
0
0
6
(1993) suggested that the mutation may induce a conformational change of the VWF subunit affecting either its sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet VWF observed in these patients.
0.6494
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
0
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al.
0.0278
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
1
(1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain.
0.0085
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
2
The proband had frequent epistaxis, easy bruising, and menorrhagia, and laboratory studies showed decreased VWF activity and decreased levels of high molecular weight multimers.
0.0248
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
3
The subtype of VWD was originally referred to as 'type IIC,' which shows recessive inheritance and an altered multimer pattern.
0.067
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
4
Further family members were heterozygous for the mutation and were phenotypically normal or only mildly affected, in accordance with the recessive pattern of inheritance.
0.0074
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
5
(2006) stated that the subtype previously known as VWD IIC is due to mutations in the VWF propeptide that prevent multimerization of VWF in the Golgi apparatus.
0.0938
no_evidence
0
0
None
SCV000020476
VCV000000305
RCV000000332
305
NM_000552.5(VWF):c.1648G>A (p.Gly550Arg)
12
6,057,930
6,057,930
C
T
Pathogenic
pathogenic
OMIM
VWF
In a German woman with von Willebrand disease type 2 (613554), referred to as type IIC, Schneppenheim et al. (1995) identified a homozygous 1898G-A transition in exon 14 of the VWF gene, resulting in a gly550-to-arg (G550R) substitution in the D2 domain. The proband had frequent epistaxis, easy bruising, and menorrhagi...
2006-10-01
2006-10-01
no assertion criteria provided
variation to disease
VWF
550
G
R
functional
null
false
0.0938
null
0
0
6
This form is now referred to as VWD type 2A.
0.0626
no_evidence
0
0
None
SCV000020488
VCV000000316
RCV000000344
316
NM_000552.5(VWF):c.1071C>A (p.Tyr357Ter)
12
6,072,369
6,072,369
G
T
Pathogenic
pathogenic
OMIM
VWF
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160....
2002-11-01
2002-11-01
no assertion criteria provided
variation to disease
VWF
357
Y
X
functional
null
false
0.067
null
0
0
0
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al.
0.067
no_evidence
0
0
None
SCV000020488
VCV000000316
RCV000000344
316
NM_000552.5(VWF):c.1071C>A (p.Tyr357Ter)
12
6,072,369
6,072,369
G
T
Pathogenic
pathogenic
OMIM
VWF
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160....
2002-11-01
2002-11-01
no assertion criteria provided
variation to disease
VWF
357
Y
X
functional
null
false
0.067
null
0
0
1
(2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160.0036) substitution.
0.0179
no_evidence
0
0
None
SCV000020488
VCV000000316
RCV000000344
316
NM_000552.5(VWF):c.1071C>A (p.Tyr357Ter)
12
6,072,369
6,072,369
G
T
Pathogenic
pathogenic
OMIM
VWF
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160....
2002-11-01
2002-11-01
no assertion criteria provided
variation to disease
VWF
357
Y
X
functional
null
false
0.067
null
0
0
2
The authors noted that the Y357X mutation is a type 3 mutation (277480) presumably because it represents a truncating mutation and lack of protein expression.
0.0192
no_evidence
0
0
None
SCV000020488
VCV000000316
RCV000000344
316
NM_000552.5(VWF):c.1071C>A (p.Tyr357Ter)
12
6,072,369
6,072,369
G
T
Pathogenic
pathogenic
OMIM
VWF
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160....
2002-11-01
2002-11-01
no assertion criteria provided
variation to disease
VWF
357
Y
X
functional
null
false
0.067
null
0
0
3
The patient had very low levels of VWF and F8, and absent binding of VWF to F8.
0.037
no_evidence
0
0
None
SCV000020488
VCV000000316
RCV000000344
316
NM_000552.5(VWF):c.1071C>A (p.Tyr357Ter)
12
6,072,369
6,072,369
G
T
Pathogenic
pathogenic
OMIM
VWF
In a 20-year-old French woman with VWD type 2N (see 613554), Mazurier et al. (2002) identified compound heterozygosity for 2 mutations in the VWF gene: a 1071C-A transversion in exon 9, resulting in a tyr357-to-ter (Y357X) substitution, and a 3178T-C transition in exon 24, resulting in a cys1060-to-arg (C1060R; 613160....
2002-11-01
2002-11-01
no assertion criteria provided
variation to disease
VWF
357
Y
X
functional
null
false
0.067
null
0
0
4
The diagnosis was complicated at first because 2 male first cousins had F8 deficiency (306700) due to a hemizygous mutation in the F8 gene (C179G; 300841.0268).
0.0154
no_evidence
0
0
None
SCV000020491
VCV000000319
RCV000000347
319
NM_012338.4(TSPAN12):c.709G>C (p.Ala237Pro)
7
120,788,801
120,788,801
C
G
Pathogenic
pathogenic
OMIM
TSPAN12
In affected members of 4 unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy-5 (EVR5; 613310), Nikopoulos et al. (2010) identified heterozygosity for a 709G-C transversion in exon 8 of the TSPAN12 gene, resulting in an ala237-to-pro (A237P) substitution at a highly conserved residue in a...
2010-02-12
2010-02-12
no assertion criteria provided
variation to disease
TSPAN12
237
A
P
functional
null
false
0.0164
null
0
0
0
In affected members of 4 unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy-5 (EVR5; 613310), Nikopoulos et al.
0.0164
no_evidence
0
0
None
SCV000020491
VCV000000319
RCV000000347
319
NM_012338.4(TSPAN12):c.709G>C (p.Ala237Pro)
7
120,788,801
120,788,801
C
G
Pathogenic
pathogenic
OMIM
TSPAN12
In affected members of 4 unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy-5 (EVR5; 613310), Nikopoulos et al. (2010) identified heterozygosity for a 709G-C transversion in exon 8 of the TSPAN12 gene, resulting in an ala237-to-pro (A237P) substitution at a highly conserved residue in a...
2010-02-12
2010-02-12
no assertion criteria provided
variation to disease
TSPAN12
237
A
P
functional
null
false
0.0164
null
0
0
1
(2010) identified heterozygosity for a 709G-C transversion in exon 8 of the TSPAN12 gene, resulting in an ala237-to-pro (A237P) substitution at a highly conserved residue in an alpha-helical structure within the fourth transmembrane domain.
0.0053
no_evidence
0
0
None
SCV000020491
VCV000000319
RCV000000347
319
NM_012338.4(TSPAN12):c.709G>C (p.Ala237Pro)
7
120,788,801
120,788,801
C
G
Pathogenic
pathogenic
OMIM
TSPAN12
In affected members of 4 unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy-5 (EVR5; 613310), Nikopoulos et al. (2010) identified heterozygosity for a 709G-C transversion in exon 8 of the TSPAN12 gene, resulting in an ala237-to-pro (A237P) substitution at a highly conserved residue in a...
2010-02-12
2010-02-12
no assertion criteria provided
variation to disease
TSPAN12
237
A
P
functional
null
false
0.0164
null
0
0
2
The mutation was not detected in 140 ethnically matched controls, but was found in 3 relatives of uncertain clinical status and in 1 healthy individual, suggesting nonpenetrance.
0.0045
no_evidence
0
0
None
SCV000020491
VCV000000319
RCV000000347
319
NM_012338.4(TSPAN12):c.709G>C (p.Ala237Pro)
7
120,788,801
120,788,801
C
G
Pathogenic
pathogenic
OMIM
TSPAN12
In affected members of 4 unrelated Dutch families segregating autosomal dominant exudative vitreoretinopathy-5 (EVR5; 613310), Nikopoulos et al. (2010) identified heterozygosity for a 709G-C transversion in exon 8 of the TSPAN12 gene, resulting in an ala237-to-pro (A237P) substitution at a highly conserved residue in a...
2010-02-12
2010-02-12
no assertion criteria provided
variation to disease
TSPAN12
237
A
P
functional
null
false
0.0164
null
0
0
3
Genealogic analysis revealed that ancestors of 3 of the 4 families were born in the same eastern region of The Netherlands, and microsatellite marker analysis demonstrated a shared haplotype among all 4 families, suggesting that A237P is a regional founder mutation.
0.0059
no_evidence
0
0
None
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
0
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al.
0.2593
no_evidence
0
0
None
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
1
(1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2A gene, resulting in a cys107-to-arg (C107R) substitution in the mature protein.
0.0091
no_evidence
0
0
None
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
2
(1992) found the same mutation, which resulted in a cys138-to-arg (C138R) substitution in a different numbering system.
0.0164
no_evidence
0
0
None
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
3
Expression studies of the mutant supported the view that the point mutation was responsible for the disease phenotype.
0.9962
has_evidence
0.0061
0.9939
PS3
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
4
(Mahuran (1994) pointed out that the mutations identified by Schroder et al.
0.7954
no_evidence
0
0
None
SCV000020565
VCV000000390
RCV000000421
390
NM_000405.5(GM2A):c.412T>C (p.Cys138Arg)
5
151,266,899
151,266,899
T
C
Pathogenic
pathogenic
OMIM
GM2A
In cultured fibroblasts derived from a black female infant, born of unrelated parents, with immunologically proven GM2 activator protein deficiency (272750), who was reported by de Baecque et al. (1975), Schroder et al. (1991) identified a homozygous 412T-C transition (counted from A of the initiation codon) in the GM2...
1992-05-01
1992-05-01
no assertion criteria provided
variation to disease
GM2A
138
C
R
functional
PS3
true
0.9962
PS3
0.9939
0
5
(1992) (CYS138ARG) are the same but derived from different amino acid numbering systems.)
0.0053
no_evidence
0
0
None
SCV000020566
VCV000000391
RCV000000422
391
NM_000405.5(GM2A):c.506G>C (p.Arg169Pro)
5
151,267,375
151,267,375
G
C
Pathogenic
pathogenic
OMIM
GM2A
In an infant with variant AB of GM2-gangliosidosis (272750), Schroder et al. (1993) identified a 506G-C transversion in the GM2A gene, resulting in substitution of proline for arginine-169 (R169P). The patient was homozygous, whereas both parents were heterozygous. Other studies suggested that the R169P mutation result...
1993-11-01
1993-11-01
no assertion criteria provided
variation to disease
GM2A
169
R
P
functional
PS3
true
0.9935
PS3
0.9954
0
0
In an infant with variant AB of GM2-gangliosidosis (272750), Schroder et al.
0.0979
no_evidence
0
0
None
SCV000020566
VCV000000391
RCV000000422
391
NM_000405.5(GM2A):c.506G>C (p.Arg169Pro)
5
151,267,375
151,267,375
G
C
Pathogenic
pathogenic
OMIM
GM2A
In an infant with variant AB of GM2-gangliosidosis (272750), Schroder et al. (1993) identified a 506G-C transversion in the GM2A gene, resulting in substitution of proline for arginine-169 (R169P). The patient was homozygous, whereas both parents were heterozygous. Other studies suggested that the R169P mutation result...
1993-11-01
1993-11-01
no assertion criteria provided
variation to disease
GM2A
169
R
P
functional
PS3
true
0.9935
PS3
0.9954
0
1
(1993) identified a 506G-C transversion in the GM2A gene, resulting in substitution of proline for arginine-169 (R169P).
0.0217
no_evidence
0
0
None
SCV000020566
VCV000000391
RCV000000422
391
NM_000405.5(GM2A):c.506G>C (p.Arg169Pro)
5
151,267,375
151,267,375
G
C
Pathogenic
pathogenic
OMIM
GM2A
In an infant with variant AB of GM2-gangliosidosis (272750), Schroder et al. (1993) identified a 506G-C transversion in the GM2A gene, resulting in substitution of proline for arginine-169 (R169P). The patient was homozygous, whereas both parents were heterozygous. Other studies suggested that the R169P mutation result...
1993-11-01
1993-11-01
no assertion criteria provided
variation to disease
GM2A
169
R
P
functional
PS3
true
0.9935
PS3
0.9954
0
2
Other studies suggested that the R169P mutation resulted in premature degradation of the mutant GM2 activator, either during the posttranslational processing steps or after reaching the lysosome.
0.9935
has_evidence
0.0046
0.9954
PS3
SCV000020566
VCV000000391
RCV000000422
391
NM_000405.5(GM2A):c.506G>C (p.Arg169Pro)
5
151,267,375
151,267,375
G
C
Pathogenic
pathogenic
OMIM
GM2A
In an infant with variant AB of GM2-gangliosidosis (272750), Schroder et al. (1993) identified a 506G-C transversion in the GM2A gene, resulting in substitution of proline for arginine-169 (R169P). The patient was homozygous, whereas both parents were heterozygous. Other studies suggested that the R169P mutation result...
1993-11-01
1993-11-01
no assertion criteria provided
variation to disease
GM2A
169
R
P
functional
PS3
true
0.9935
PS3
0.9954
0
3
With other mutations, the phenotype appears to be due to inactivation of the physiologic activator function.
0.7562
no_evidence
0
0
None
SCV000020569
VCV000000394
RCV000000425
394
NM_000405.5(GM2A):c.160G>T (p.Glu54Ter)
5
151,259,833
151,259,833
G
T
Pathogenic
pathogenic
OMIM
GM2A
Chen et al. (1999) studied a Laotian child with the AB variant form of GM2-gangliosidosis (272750) and identified a 160G-T transversion in the GM2A gene, resulting in a glu54-to-ter (E54X) substitution.
1999-07-01
1999-07-01
no assertion criteria provided
variation to disease
GM2A
54
E
X
functional
null
false
0.0592
null
0
0
0
(1999) studied a Laotian child with the AB variant form of GM2-gangliosidosis (272750) and identified a 160G-T transversion in the GM2A gene, resulting in a glu54-to-ter (E54X) substitution.
0.0592
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
0
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al.
0.1327
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
1
(2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein.
0.0136
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
2
At 3 weeks of age, he became hypoactive and sucked poorly.
0.6318
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
3
Physical examination revealed macrocephaly, a weak cry, wide anterior fontanel, and axial hypotonia.
0.2176
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
4
He had intermittent generalized tonic movements, and funduscopy showed pallor of the optic discs.
0.1932
no_evidence
0
0
None
SCV000020600
VCV000000423
RCV000000451
423
NM_199069.2(NDUFAF3):c.365G>C (p.Arg122Pro)
3
49,022,903
49,022,903
G
C
Pathogenic
pathogenic
OMIM
NDUFAF3
In a male infant with severe mitochondrial complex I deficiency nuclear type 18 (MC1DN18; 618240), Saada et al. (2009) identified a homozygous 365G-C transversion in the NDUFAF3 gene, resulting in an arg122-to-pro (R122P) substitution at the C-terminal end of the protein. The child was born of consanguineous Arab Musli...
2009-06-01
2009-06-01
no assertion criteria provided
variation to disease
NDUFAF3
122
R
P
functional
null
false
0.6318
null
0
0
5
At 3 months of age, there was no eye contact and marked axial hypotonia with brisk tendon reflexes.
0.4236
no_evidence
0
0
None
SCV000020618
VCV000000440
RCV000000469
440
NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)
19
44,813,527
44,813,527
C
T
Pathogenic
pathogenic
OMIM
BCAM
In an English woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2007) identified compound heterozygosity for 2 mutations in the BCAM gene: a 691C-T transition in exon 6 resulting in an arg231-to-ter (R231X) substitution in the extracellular second immunoglobulin domain, and a deletion ...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
231
R
X
functional
null
false
0.0311
null
0
0
0
In an English woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al.
0.0233
no_evidence
0
0
None
SCV000020618
VCV000000440
RCV000000469
440
NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)
19
44,813,527
44,813,527
C
T
Pathogenic
pathogenic
OMIM
BCAM
In an English woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2007) identified compound heterozygosity for 2 mutations in the BCAM gene: a 691C-T transition in exon 6 resulting in an arg231-to-ter (R231X) substitution in the extracellular second immunoglobulin domain, and a deletion ...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
231
R
X
functional
null
false
0.0311
null
0
0
1
(2007) identified compound heterozygosity for 2 mutations in the BCAM gene: a 691C-T transition in exon 6 resulting in an arg231-to-ter (R231X) substitution in the extracellular second immunoglobulin domain, and a deletion of exons 3 and 4 (612773.0004).
0.0186
no_evidence
0
0
None
SCV000020618
VCV000000440
RCV000000469
440
NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)
19
44,813,527
44,813,527
C
T
Pathogenic
pathogenic
OMIM
BCAM
In an English woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2007) identified compound heterozygosity for 2 mutations in the BCAM gene: a 691C-T transition in exon 6 resulting in an arg231-to-ter (R231X) substitution in the extracellular second immunoglobulin domain, and a deletion ...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
231
R
X
functional
null
false
0.0311
null
0
0
2
The woman had previously been reported by Darnborough et al.
0.0311
no_evidence
0
0
None
SCV000020618
VCV000000440
RCV000000469
440
NM_005581.5(BCAM):c.691C>T (p.Arg231Ter)
19
44,813,527
44,813,527
C
T
Pathogenic
pathogenic
OMIM
BCAM
In an English woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2007) identified compound heterozygosity for 2 mutations in the BCAM gene: a 691C-T transition in exon 6 resulting in an arg231-to-ter (R231X) substitution in the extracellular second immunoglobulin domain, and a deletion ...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
231
R
X
functional
null
false
0.0311
null
0
0
3
There were no clinical manifestations; she was identified through routine serology in preparation for surgery.
0.0136
no_evidence
0
0
None
SCV000020620
VCV000000442
RCV000000471
442
NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)
19
44,813,547
44,813,547
C
A
Pathogenic
pathogenic
OMIM
BCAM
In a healthy Japanese man with the Lutheran null blood group phenotype (247420), Mallinson et al. (1997) identified a homozygous 733C-A transversion in exon 6 of the BCAM gene, resulting in a cys237-to-ter (C237X) substitution in the extracellular domain. He was identified through blood donation and had no phenotypic m...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
237
C
X
functional
null
false
0.0438
null
0
0
0
In a healthy Japanese man with the Lutheran null blood group phenotype (247420), Mallinson et al.
0.0214
no_evidence
0
0
None
SCV000020620
VCV000000442
RCV000000471
442
NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)
19
44,813,547
44,813,547
C
A
Pathogenic
pathogenic
OMIM
BCAM
In a healthy Japanese man with the Lutheran null blood group phenotype (247420), Mallinson et al. (1997) identified a homozygous 733C-A transversion in exon 6 of the BCAM gene, resulting in a cys237-to-ter (C237X) substitution in the extracellular domain. He was identified through blood donation and had no phenotypic m...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
237
C
X
functional
null
false
0.0438
null
0
0
1
(1997) identified a homozygous 733C-A transversion in exon 6 of the BCAM gene, resulting in a cys237-to-ter (C237X) substitution in the extracellular domain.
0.0126
no_evidence
0
0
None
SCV000020620
VCV000000442
RCV000000471
442
NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)
19
44,813,547
44,813,547
C
A
Pathogenic
pathogenic
OMIM
BCAM
In a healthy Japanese man with the Lutheran null blood group phenotype (247420), Mallinson et al. (1997) identified a homozygous 733C-A transversion in exon 6 of the BCAM gene, resulting in a cys237-to-ter (C237X) substitution in the extracellular domain. He was identified through blood donation and had no phenotypic m...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
237
C
X
functional
null
false
0.0438
null
0
0
2
He was identified through blood donation and had no phenotypic manifestations.
0.0053
no_evidence
0
0
None
SCV000020620
VCV000000442
RCV000000471
442
NM_005581.5(BCAM):c.711C>A (p.Cys237Ter)
19
44,813,547
44,813,547
C
A
Pathogenic
pathogenic
OMIM
BCAM
In a healthy Japanese man with the Lutheran null blood group phenotype (247420), Mallinson et al. (1997) identified a homozygous 733C-A transversion in exon 6 of the BCAM gene, resulting in a cys237-to-ter (C237X) substitution in the extracellular domain. He was identified through blood donation and had no phenotypic m...
2007-03-01
2007-03-01
no assertion criteria provided
variation to disease
BCAM
237
C
X
functional
null
false
0.0438
null
0
0
3
(2007) stated that the C237X substitution resulted from a 711C-A transversion based on numbering from the translation initiation ATG codon.
0.0438
no_evidence
0
0
None
SCV000020621
VCV000000443
RCV000000472
443
NM_005581.5(BCAM):c.361C>T (p.Arg121Ter)
19
44,812,319
44,812,319
C
T
Pathogenic
pathogenic
OMIM
BCAM
In a German Caucasian woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2004) identified a homozygous 361C-T transition in exon 3 of the BCAM gene, resulting in an arg121-to-ter (R121X) substitution in the extracellular first immunoglobulin domain. She was identified in a surgical work...
2018-08-28
2018-08-28
no assertion criteria provided
variation to disease
BCAM
121
R
X
functional
null
false
0.0162
null
0
0
0
In a German Caucasian woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al.
0.0162
no_evidence
0
0
None
SCV000020621
VCV000000443
RCV000000472
443
NM_005581.5(BCAM):c.361C>T (p.Arg121Ter)
19
44,812,319
44,812,319
C
T
Pathogenic
pathogenic
OMIM
BCAM
In a German Caucasian woman with the Lutheran null blood group phenotype (247420), Karamatic Crew et al. (2004) identified a homozygous 361C-T transition in exon 3 of the BCAM gene, resulting in an arg121-to-ter (R121X) substitution in the extracellular first immunoglobulin domain. She was identified in a surgical work...
2018-08-28
2018-08-28
no assertion criteria provided
variation to disease
BCAM
121
R
X
functional
null
false
0.0162
null
0
0
1
(2004) identified a homozygous 361C-T transition in exon 3 of the BCAM gene, resulting in an arg121-to-ter (R121X) substitution in the extracellular first immunoglobulin domain.
0.0084
no_evidence
0
0
None
SCV000020634
VCV000000456
RCV000000485
456
NM_000097.7(CPOX):c.883C>G (p.His295Asp)
3
98,588,783
98,588,783
G
C
Pathogenic
pathogenic
OMIM
CPOX
Lamoril et al. (1997) demonstrated a novel mutation in the CPO gene in each of 3 unrelated patients with hereditary coproporphyria (HCP; 121300). The diagnosis was based on the observation of typical clinical manifestations, increased excretions of delta-aminolevulinic acid and porphobilinogen in urine and coproporphyr...
1997-01-01
1997-01-01
no assertion criteria provided
variation to disease
CPOX
295
H
D
functional
null
false
0.2625
null
0
0
0
(1997) demonstrated a novel mutation in the CPO gene in each of 3 unrelated patients with hereditary coproporphyria (HCP; 121300).
0.0155
no_evidence
0
0
None
SCV000020634
VCV000000456
RCV000000485
456
NM_000097.7(CPOX):c.883C>G (p.His295Asp)
3
98,588,783
98,588,783
G
C
Pathogenic
pathogenic
OMIM
CPOX
Lamoril et al. (1997) demonstrated a novel mutation in the CPO gene in each of 3 unrelated patients with hereditary coproporphyria (HCP; 121300). The diagnosis was based on the observation of typical clinical manifestations, increased excretions of delta-aminolevulinic acid and porphobilinogen in urine and coproporphyr...
1997-01-01
1997-01-01
no assertion criteria provided
variation to disease
CPOX
295
H
D
functional
null
false
0.2625
null
0
0
1
The diagnosis was based on the observation of typical clinical manifestations, increased excretions of delta-aminolevulinic acid and porphobilinogen in urine and coproporphyrin III in both feces and urine, and 50% decreased COX activity in lymphocytes.
0.2625
no_evidence
0
0
None
SCV000020634
VCV000000456
RCV000000485
456
NM_000097.7(CPOX):c.883C>G (p.His295Asp)
3
98,588,783
98,588,783
G
C
Pathogenic
pathogenic
OMIM
CPOX
Lamoril et al. (1997) demonstrated a novel mutation in the CPO gene in each of 3 unrelated patients with hereditary coproporphyria (HCP; 121300). The diagnosis was based on the observation of typical clinical manifestations, increased excretions of delta-aminolevulinic acid and porphobilinogen in urine and coproporphyr...
1997-01-01
1997-01-01
no assertion criteria provided
variation to disease
CPOX
295
H
D
functional
null
false
0.2625
null
0
0
2
One patient had a C-to-G transversion at nucleotide 883 in exon 4 that resulted in a his295-to-asp (H295D) substitution.
0.0051
no_evidence
0
0
None
SCV000020638
VCV000000460
RCV000000489
460
NM_000097.7(CPOX):c.623C>T (p.Ser208Phe)
3
98,591,089
98,591,089
G
A
Pathogenic
pathogenic
OMIM
CPOX
Wiman et al. (2002) identified a heterozygous 623C-T mutation in exon 2 of the CPO gene, resulting in a ser208-to-phe (S208F) substitution, in a patient with hereditary coproporphyria (HCP; 121300).
2002-01-01
2002-01-01
no assertion criteria provided
variation to disease
CPOX
208
S
F
functional
null
false
0.0179
null
0
0
0
(2002) identified a heterozygous 623C-T mutation in exon 2 of the CPO gene, resulting in a ser208-to-phe (S208F) substitution, in a patient with hereditary coproporphyria (HCP; 121300).
0.0179
no_evidence
0
0
None
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
0
(2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300).
0.0153
no_evidence
0
0
None
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
1
However, a greater than expected increase in ALA compared with PBG and a substantial increase in erythrocyte zinc protoporphyrin suggested additional ALA dehydratase (ALAD) deficiency (612740).
0.0572
no_evidence
0
0
None
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
2
(2006) detected a heterozygous G-to-C transversion at nucleotide 835 of the CPO gene that caused a gly279-to-arg (G279R) amino acid change.
0.011
no_evidence
0
0
None
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
3
The mutant protein expressed in E. coli was unstable and produced about 5% of activity compared with the wildtype.
0.9963
has_evidence
0.0073
0.9927
PS3
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
4
A missense mutation was found on 1 allele of the ALAD gene (125270.0006).
0.0102
no_evidence
0
0
None
SCV000020641
VCV000000463
RCV000000492
463
NM_000097.7(CPOX):c.835G>C (p.Gly279Arg)
3
98,588,831
98,588,831
C
G
Pathogenic
pathogenic
OMIM
CPOX
Akagi et al. (2006) described a Caucasian male who had symptoms of acute porphyria, with increases in urinary delta-aminolevulinic acid (ALA), porphobilinogen (PBG), and coproporphyrin that were consistent with hereditary coproporphyria (HCP; 121300). However, a greater than expected increase in ALA compared with PBG a...
2006-01-01
2006-01-01
no assertion criteria provided
variation to disease
CPOX
279
G
R
functional
PS3
true
0.9963
PS3
0.9927
0
5
Thus, the patient represented the first case of porphyria in which both CPO and ALAD deficiencies were demonstrated at the molecular level.
0.0221
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
0
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al.
0.0588
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
1
(1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2.
0.0441
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
2
The deficiency of the 2.1 ankyrin isoform was accompanied by a proportional deficiency of spectrin.
0.1302
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
3
The genetic defect was a nonsense mutation glu1669-to-ter (GAA-to-TAA) in 1 allele of the ANK1 gene.
0.0672
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
4
Only normal 2.1 mRNA was detected in the reticulocyte RNA.
0.9404
has_evidence
0.1528
0.8472
PS3
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
5
The regulatory domain of ankyrin is subject to extensive alternative splicing.
0.0283
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
6
In the case of this mutation, alternative splicing within the regulatory domain of ankyrin retained codon 1669 in ankyrin 2.1 mRNA and removed it from ankyrin 2.2 mRNA.
0.0519
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
7
(1995) proposed that the glu1669-to-ter mutation decreased the stability of the abnormal ankyrin 2.1 mRNA allele, leading to a decreased synthesis of ankyrin 2.1 and a secondary deficiency of spectrin.
0.6315
no_evidence
0
0
None
SCV000020684
VCV000000506
RCV000000535
506
NM_000037.4(ANK1):c.5005G>T (p.Glu1669Ter)
8
41,672,445
41,672,445
C
A
Pathogenic
pathogenic
OMIM
ANK1
In a kindred with autosomal dominant hereditary spherocytosis (SPH1; 182900), Jarolim et al. (1995) identified a unique mutation in the regulatory domain of ankyrin associated with a marked and selective deficiency of ankyrin isoform 2.1 and a normal content of ankyrin isoform 2.2. The deficiency of the 2.1 ankyrin iso...
1995-03-01
1995-03-01
no assertion criteria provided
variation to disease
ANK1
1,669
E
X
functional
PS3
true
0.9404
PS3
0.8472
0
8
The mutant ankyrin was named for the city of origin, Rakovnik, in the Czech Republic.
0.0511
no_evidence
0
0
None
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
0
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al.
0.0218
no_evidence
0
0
None
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
1
(2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in a highly conserved residue.
0.0056
no_evidence
0
0
None
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
2
The mutation was not present in 100 control Lebanese chromosomes.
0.0041
no_evidence
0
0
None
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
3
The patients presented in infancy with focal seizures, decreased movement and strength, ataxia, lactic acidosis, and neuroimaging results consistent with Leigh syndrome.
0.0933
no_evidence
0
0
None
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
4
Biochemical studies showed complex I deficiency in liver, muscle, and fibroblasts.
0.9908
has_evidence
0.006
0.994
PS3
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
5
(2011) demonstrated that the c.296A-G transition causes a splicing defect that results in the loss of isoform 1 transcripts (Gln99ArgfsTer3).
0.9401
has_evidence
0.0113
0.9887
PS3
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
6
Fibroblasts derived from the patients reported by Pagliarini et al.
0.9418
has_evidence
0.021
0.979
PS3
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
7
(2008) had reduced steady-state levels of complex I and decreased levels of NDUFAF6 isoform 1.
0.8637
has_evidence
0.0089
0.9911
PS3
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
8
The complex I defect could be rescued by complementation with wildtype NDUFAF6.
0.9896
has_evidence
0.0153
0.9847
PS3
SCV000020726
VCV000000547
RCV000000577
547
NM_152416.4(NDUFAF6):c.296A>G (p.Gln99Arg)
8
95,032,093
95,032,093
A
G
Pathogenic
pathogenic
OMIM
NDUFAF6
In 2 Lebanese sibs, born of consanguineous parents, with mitochondrial complex I deficiency nuclear type 17 (MC1DN17; 618239) manifesting as Leigh syndrome (see 256000), Pagliarini et al. (2008) identified a homozygous c.296A-G transition in exon 2 of the NDUFAF6 gene, resulting in a gln99-to-arg (Q99R) substitution in...
2008-07-11
2008-07-11
no assertion criteria provided
variation to disease
NDUFAF6
99
Q
R
functional
PS3
true
0.9908
PS3
0.9945
0
9
Patient cells also showed decreased levels of the mtDNA-encoded subunit ND1 (MTND1; 516000) due to a translation defect, which resulted in the stalled assembly of other subunits during complex I formation.
0.8938
has_evidence
0.0055
0.9945
PS3
SCV000020941
VCV000000755
RCV000000791
755
NM_001103146.3(GIGYF2):c.1818C>G (p.Asp606Glu)
2
232,809,731
232,809,731
C
G
risk factor
risk factor
OMIM
GIGYF2
In a French mother and son with Parkinson disease-11 (PARK11; 607688), Lautier et al. (2008) identified a heterozygous 1818C-G transversion in exon 14 of the GIGYF2 gene, resulting in an asp606-to-glu (D606E) substitution in a highly conserved region. Disease onset was at ages 83 and 42, respectively. A maternal aunt, ...
2008-04-01
2008-04-01
no assertion criteria provided
variation to disease
GIGYF2
606
D
E
functional
null
false
0.0319
null
0
0
0
In a French mother and son with Parkinson disease-11 (PARK11; 607688), Lautier et al.
0.0319
no_evidence
0
0
None
SCV000020941
VCV000000755
RCV000000791
755
NM_001103146.3(GIGYF2):c.1818C>G (p.Asp606Glu)
2
232,809,731
232,809,731
C
G
risk factor
risk factor
OMIM
GIGYF2
In a French mother and son with Parkinson disease-11 (PARK11; 607688), Lautier et al. (2008) identified a heterozygous 1818C-G transversion in exon 14 of the GIGYF2 gene, resulting in an asp606-to-glu (D606E) substitution in a highly conserved region. Disease onset was at ages 83 and 42, respectively. A maternal aunt, ...
2008-04-01
2008-04-01
no assertion criteria provided
variation to disease
GIGYF2
606
D
E
functional
null
false
0.0319
null
0
0
1
(2008) identified a heterozygous 1818C-G transversion in exon 14 of the GIGYF2 gene, resulting in an asp606-to-glu (D606E) substitution in a highly conserved region.
0.009
no_evidence
0
0
None
SCV000021053
VCV000000855
RCV000000903
855
NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys)
17
28,405,360
28,405,360
G
A
Pathogenic
pathogenic
OMIM
SLC46A1
In a patient with hereditary folate malabsorption (229050), Lasry et al. (2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3. In vitro functional expression stud...
2008-09-01
2008-09-01
no assertion criteria provided
variation to disease
SLC46A1
113
R
C
functional
PS3
true
0.9978
PS3
0.9944
0
0
In a patient with hereditary folate malabsorption (229050), Lasry et al.
0.1223
no_evidence
0
0
None
SCV000021053
VCV000000855
RCV000000903
855
NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys)
17
28,405,360
28,405,360
G
A
Pathogenic
pathogenic
OMIM
SLC46A1
In a patient with hereditary folate malabsorption (229050), Lasry et al. (2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3. In vitro functional expression stud...
2008-09-01
2008-09-01
no assertion criteria provided
variation to disease
SLC46A1
113
R
C
functional
PS3
true
0.9978
PS3
0.9944
0
1
(2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3.
0.0063
no_evidence
0
0
None
SCV000021053
VCV000000855
RCV000000903
855
NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys)
17
28,405,360
28,405,360
G
A
Pathogenic
pathogenic
OMIM
SLC46A1
In a patient with hereditary folate malabsorption (229050), Lasry et al. (2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3. In vitro functional expression stud...
2008-09-01
2008-09-01
no assertion criteria provided
variation to disease
SLC46A1
113
R
C
functional
PS3
true
0.9978
PS3
0.9944
0
2
In vitro functional expression studies in Chinese hamster ovary (CHO) cells showed that the mutant protein was targeted to the plasma membrane but had significantly impaired folate transport activity.
0.9978
has_evidence
0.0056
0.9944
PS3
SCV000021053
VCV000000855
RCV000000903
855
NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys)
17
28,405,360
28,405,360
G
A
Pathogenic
pathogenic
OMIM
SLC46A1
In a patient with hereditary folate malabsorption (229050), Lasry et al. (2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3. In vitro functional expression stud...
2008-09-01
2008-09-01
no assertion criteria provided
variation to disease
SLC46A1
113
R
C
functional
PS3
true
0.9978
PS3
0.9944
0
3
Another mutation at this codon (R113S; 611672.0003) was identified in another patient with the disorder.
0.0061
no_evidence
0
0
None
SCV000021053
VCV000000855
RCV000000903
855
NM_080669.6(SLC46A1):c.337C>T (p.Arg113Cys)
17
28,405,360
28,405,360
G
A
Pathogenic
pathogenic
OMIM
SLC46A1
In a patient with hereditary folate malabsorption (229050), Lasry et al. (2008) identified a homozygous 337C-T transition in exon 2 of the in the SLC46A1 gene, resulting in an arg113-to-cys (R113C) substitution in the first intracellular loop connecting transmembrane helices 2 and 3. In vitro functional expression stud...
2008-09-01
2008-09-01
no assertion criteria provided
variation to disease
SLC46A1
113
R
C
functional
PS3
true
0.9978
PS3
0.9944
0
4
Bioinformatic analysis showed that the arg113 residue is highly conserved and faces the intramembrane hydrophobic pocket that may be part of a folate translocation pore.
0.0067
no_evidence
0
0
None
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