sentence stringlengths 61 1.36k | pmcid int32 162k 8.8M | gene1 stringclasses 381
values | gene2 stringclasses 392
values | variant1 stringclasses 689
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The T338I and @VARIANT$ variants affect the conserved central coiled-coil rod domain of the protein mediating dimerization; therefore, we suggest their potential deleterious effect on the protein. In the individual carrying the P505L NEFH variant, an additional novel alteration (C335R) was detected in the @GENE$ gene. ... | 6,707,335 | GRN;1577 | SQSTM1;31202 | R148P;tmVar:p|SUB|R|148|P;HGVS:p.R148P;VariantGroup:14;CorrespondingGene:2521;RS#:773655049 | E389Q;tmVar:p|SUB|E|389|Q;HGVS:p.E389Q;VariantGroup:24;CorrespondingGene:8878;RS#:1391182750 | 0no label |
c, d) Sequence chromatograms indicating the wild-type, homozygous affected and heterozygous carrier forms of c) the C to T transition at position c.229 changing the arginine residue to cysteine at position 77 of the @GENE$ protein (@VARIANT$; p.R77C) and d) the @VARIANT$ (p.I80Gfs*13) in S100A13. Mutation name is based... | 6,637,284 | S100A3;2223 | S100A13;7523 | c.229C>T;tmVar:c|SUB|C|229|T;HGVS:c.229C>T;VariantGroup:3;CorrespondingGene:6274;RS#:138355706;CA#:1116284 | c.238-241delATTG;tmVar:c|DEL|238_241|ATTG;HGVS:c.238_241delATTG;VariantGroup:13;CorrespondingGene:6284 | 0no label |
We identified four genetic variants (@GENE$-@VARIANT$, KCNH2-p.C108Y, @GENE$-p.K897T, and KCNE1-@VARIANT$) in an LQTS family. | 5,578,023 | KCNQ1;85014 | KCNH2;201 | p.R583H;tmVar:p|SUB|R|583|H;HGVS:p.R583H;VariantGroup:4;CorrespondingGene:3784;RS#:199473482;CA#:6304 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/@GENE$ (@VARIANT$; p.Ala253Thr of NELF and c.488_490delGTT; p.Cys163del of KAL1) and @GENE$/TACR3 (c. 1160-13C>T of NELF and c.824G>A; @VARIANT$ of TACR3). | 3,888,818 | KAL1;55445 | NELF;10648 | c.757G>A;tmVar:c|SUB|G|757|A;HGVS:c.757G>A;VariantGroup:3;CorrespondingGene:26012;RS#:142726563;CA#:5370407 | p.Trp275X;tmVar:p|SUB|W|275|X;HGVS:p.W275X;VariantGroup:1;CorrespondingGene:6870;RS#:144292455;CA#:144871 | 0no label |
In a second example, we identified a monoallelic change in @GENE$ (c.G680A, p.Arg227Gln, @VARIANT$:G>A), in conjunction with the @VARIANT$ of @GENE$. Monoallelic inheritance of SRD5A2, although uncommon, has been reported in a severely under-virilized individual with hypospadias and bilateral inguinal testes ... | 5,765,430 | SRD5A2;37292 | SF1;138518 | rs9332964;tmVar:rs9332964;VariantGroup:0;CorrespondingGene:6716;RS#:9332964 | single amino acid deletion at position 372;tmVar:|Allele|SINGLEAMINO|372;VariantGroup:20;CorrespondingGene:7536 | 11 |
To investigate the role of @GENE$ variations along with @GENE$ mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous GJB2 mutations for variants in Cx31 by sequencing. Analysis of the entire coding region of the Cx31 gene revealed the presence of two different mis... | 2,737,700 | GJB3;7338 | GJB2;2975 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | A to G transition at nucleotide position 497;tmVar:c|SUB|A|497|G;HGVS:c.497A>G;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 0no label |
In the subject III.1, the variant, carried in the heterozygous status, is the c.868 G > T; @VARIANT$, in the glucokinase (@GENE$) gene; the III.2 subject carried the @VARIANT$; p.Pro291Arg, in the @GENE$ gene. | 8,306,687 | CGK;55964 | HNF1A;459 | p.Glu290*;tmVar:p|SUB|E|290|*;HGVS:p.E290*;VariantGroup:9;CorrespondingGene:2645 | c.872 C > G;tmVar:c|SUB|C|872|G;HGVS:c.872C>G;VariantGroup:2;CorrespondingGene:6927;RS#:193922606;CA#:214336 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (@VARIANT$) of the coding sequence in exon 7 of EDA, which results in the substitution of Gly at residue 257 to Arg. Additionally, the nucleotide sequence showed a monoallelic @VARIANT$ (c.511C>T) of the coding sequence in exon 3 of WNT10A, which resu... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | C to T transition at nucleotide 511;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
Both homozygous and compound heterozygous variants in the @GENE$ gene have been described as causative for juvenile ALS. The G1177X nonsense variant was first detected in compound heterozygous form in a family with two affected siblings suffering from infantile ascending spastic paralysis with bulbar involvement. The a... | 6,707,335 | ALS2;23264 | MATR3;7830 | P11S;tmVar:p|SUB|P|11|S;HGVS:p.P11S;VariantGroup:6;RS#:995345187 | T2583I;tmVar:p|SUB|T|2583|I;HGVS:p.T2583I;VariantGroup:31;CorrespondingGene:1778 | 0no label |
Somatic overgrowth associated with homozygous mutations in both MAN1B1 and SEC23A Using whole-exome sequencing, we identified homozygous mutations in two unlinked genes, SEC23A @VARIANT$ (p.M400I) and @GENE$ c.1000C>T (@VARIANT$), associated with congenital birth defects in two patients from a consanguineous family. Pa... | 4,853,519 | MAN1B1;5230 | SEC23A;4642 | c.1200G>C;tmVar:c|SUB|G|1200|C;HGVS:c.1200G>C;VariantGroup:0;CorrespondingGene:10484;RS#:866845715;CA#:259543384 | p.R334C;tmVar:p|SUB|R|334|C;HGVS:p.R334C;VariantGroup:4;CorrespondingGene:11253;RS#:387906886;CA#:129197 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; @VARIANT$ of @GENE$) and NELF/TACR3 (c. 1160-13C>T of @GENE$ and @VARIANT$; p.Trp275X of TACR3). | 3,888,818 | KAL1;55445 | NELF;10648 | p.Cys163del;tmVar:p|DEL|163|C;HGVS:p.163delC;VariantGroup:10;CorrespondingGene:3730 | c.824G>A;tmVar:c|SUB|G|824|A;HGVS:c.824G>A;VariantGroup:1;CorrespondingGene:26012;RS#:144292455;CA#:144871 | 0no label |
Only 9 mutations previously reported as recurrent were detected in our series of patients (i.e. 11% of the mutations), specifically, c.1996C>T, c.223delG, @VARIANT$, c.494C>T, c.3719G>A and c.5749G>T in @GENE$, c.238_239dupC in USH1C, and @VARIANT$ and c.10712C>T in @GENE$. Therefore, in the process of designing any st... | 3,125,325 | MYO7A;219 | USH2A;66151 | c.1556G>A;tmVar:c|SUB|G|1556|A;HGVS:c.1556G>A;VariantGroup:9;CorrespondingGene:4647;RS#:111033206;CA#:278629 | c.2299delG;tmVar:c|DEL|2299|G;HGVS:c.2299delG;VariantGroup:190;CorrespondingGene:7399;RS#:80338903 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/@GENE$ (c.757G>A; p.Ala253Thr of @GENE$ and c.488_490delGTT; p.Cys163del of KAL1) and NELF/TACR3 (@VARIANT$ of NELF and c.824G>A; @VARIANT$ of TACR3). | 3,888,818 | KAL1;55445 | NELF;10648 | c. 1160-13C>T;tmVar:c|SUB|C|1160-13|T;HGVS:c.1160-13C>T;VariantGroup:5;CorrespondingGene:26012;RS#:781275840;CA#:5370137 | p.Trp275X;tmVar:p|SUB|W|275|X;HGVS:p.W275X;VariantGroup:1;CorrespondingGene:6870;RS#:144292455;CA#:144871 | 0no label |
In patient AVM226, we identified the compound heterozygous variants @VARIANT$ (p.Val1259Ile) and c.2966A>T (@VARIANT$) in @GENE$ (table 2). @GENE$ and DSCAM have similar neurodevelopmental functions and are essential for self-avoidance in the developing mouse retina. | 6,161,649 | DSCAM;74393 | DSCAML1;79549 | c.3775G>A;tmVar:c|SUB|G|3775|A;HGVS:c.3775G>A;VariantGroup:5;CorrespondingGene:1826;RS#:1212415588 | p.Gln989Leu;tmVar:p|SUB|Q|989|L;HGVS:p.Q989L;VariantGroup:5;CorrespondingGene:83394;RS#:1212415588 | 0no label |
On the other hand, two missense mutations of the EPHA2 gene were identified in two families, SLC26A4: c.1300G>A (p.434A>T), EPHA2: c.1063G>A (@VARIANT$) and @GENE$: @VARIANT$ (p.410T>M), @GENE$: c.1532C>T (p.T511M) (Fig. 6a, b). | 7,067,772 | SLC26A4;20132 | EPHA2;20929 | p.G355R;tmVar:p|SUB|G|355|R;HGVS:p.G355R;VariantGroup:4;CorrespondingGene:1969;RS#:370923409;CA#:625329 | c.1229C>A;tmVar:c|SUB|C|1229|A;HGVS:c.1229C>A;VariantGroup:21;CorrespondingGene:5172 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/KAL1 (c.757G>A; p.Ala253Thr of @GENE$ and c.488_490delGTT; p.Cys163del of @GENE$) and NELF/TACR3 (@VARIANT$ of NELF and c.824G>A; @VARIANT$ of TACR3). | 3,888,818 | NELF;10648 | KAL1;55445 | c. 1160-13C>T;tmVar:c|SUB|C|1160-13|T;HGVS:c.1160-13C>T;VariantGroup:5;CorrespondingGene:26012;RS#:781275840;CA#:5370137 | p.Trp275X;tmVar:p|SUB|W|275|X;HGVS:p.W275X;VariantGroup:1;CorrespondingGene:6870;RS#:144292455;CA#:144871 | 0no label |
Two different GJB3 mutations (@VARIANT$ and A194T) occurring in compound heterozygosity with the 235delC and @VARIANT$ of @GENE$ were identified in three unrelated families (235delC/N166S, 235delC/A194T and 299delAT/A194T). Neither of these mutations in @GENE$ was detected in DNA from 200 unrelated Chinese controls. | 2,737,700 | GJB2;2975 | Cx31;7338 | N166S;tmVar:p|SUB|N|166|S;HGVS:p.N166S;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | 0no label |
Interestingly, four of these TEK mutations (p.E103D, @VARIANT$, p.Q214P, and p.G743A) co-occurred with three heterozygous mutations in another major PCG gene @GENE$ (p.A115P, p.E229K, and @VARIANT$) in five families. The parents of these probands harbored either of the heterozygous @GENE$ or CYP1B1 alleles and were asy... | 5,953,556 | CYP1B1;68035 | TEK;397 | p.I148T;tmVar:p|SUB|I|148|T;HGVS:p.I148T;VariantGroup:5;CorrespondingGene:7010;RS#:35969327;CA#:5015918 | p.R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | 0no label |
On the basis of the data collected in this study, we may speculate that the presence of @GENE$-@VARIANT$, together with three @GENE$-@VARIANT$ alleles, could lead to an increased risk of developing cardiac arrhythmias due to the prolongation of the QT interval. | 5,578,023 | KCNH2;201 | KCNE1;3753 | p.C108Y;tmVar:p|SUB|C|108|Y;HGVS:p.C108Y;VariantGroup:3;CorrespondingGene:3757 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 11 |
Moreover, patients carrying a LAMA4 @VARIANT$ mutation have a significantly reduced extracellular matrix (ECM) in cardiomyocytes. These findings support the importance of LAMA4 as a structural and signalling molecule in cardiomyocytes, and may indicate the modifier role that missense variations in LAMA4 play in the dis... | 6,359,299 | MYH7;68044 | MYBPC3;215 | Pro943Leu;tmVar:p|SUB|P|943|L;HGVS:p.P943L;VariantGroup:5;CorrespondingGene:3910;RS#:387907365;CA#:143749 | R326Q;tmVar:p|SUB|R|326|Q;HGVS:p.R326Q;VariantGroup:6;CorrespondingGene:4607;RS#:34580776;CA#:16212 | 0no label |
Moreover, this MITF variant was not detected in the 666 control chromosomes from normal hearing Korean subjects, supporting the pathogenic potential of p.R341C in @GENE$ in SH107-225. However, symptoms and signs suggesting Waardenburg syndrome type2 (WS2) including retinal abnormalities and pigmentation abnormalities c... | 4,998,745 | MITF;4892 | GJB3;7338 | p.R341C;tmVar:p|SUB|R|341|C;HGVS:p.R341C;VariantGroup:7;CorrespondingGene:161497;RS#:1359505251 | p.V193E;tmVar:p|SUB|V|193|E;HGVS:p.V193E;VariantGroup:21;CorrespondingGene:2706 | 0no label |
In patient AVM226, we identified the compound heterozygous variants c.3775G>A (p.Val1259Ile) and c.2966A>T (p.Gln989Leu) in @GENE$ (table 2). DSCAML1 and DSCAM have similar neurodevelopmental functions and are essential for self-avoidance in the developing mouse retina. In patient AVM144, the compound heterozygous ... | 6,161,649 | DSCAM;74393 | PTPN13;7909 | c.116-1G>A;tmVar:c|SUB|G|116-1|A;HGVS:c.116-1G>A;VariantGroup:5;CorrespondingGene:83394;RS#:1212415588 | p.Arg565Gln;tmVar:p|SUB|R|565|Q;HGVS:p.R565Q;VariantGroup:5;CorrespondingGene:9448;RS#:1212415588 | 0no label |
Results Family with inherited neutropaenia, monocytosis and hearing impairment associated with mutations in GFI1 and @GENE$. Pedigree, phenotypes and mutation status are indicated as per the key provided (a). Causative heterozygous mutations in @GENE$ (p.N382S/@VARIANT$) and MYO6 (@VARIANT$/c.3526A > C) were identified... | 7,026,993 | MYO6;56417 | GFI1;3854 | c.1145A > G;tmVar:c|SUB|A|1145|G;HGVS:c.1145A>G;VariantGroup:1;CorrespondingGene:2672;RS#:28936381;CA#:119872 | p.I1176L;tmVar:p|SUB|I|1176|L;HGVS:p.I1176L;VariantGroup:2;CorrespondingGene:4646;RS#:755922465;CA#:141060203 | 0no label |
The @VARIANT$ variant in GJB2 occurring in complex heterozygosity with a pathogenic @GENE$ variant, @VARIANT$ from SH175-389, suggests a possible digenic etiology of SNHL involving two different gap junction proteins, @GENE$ and Cx31. | 4,998,745 | GJB3;7338 | Cx26;2975 | p.V193E;tmVar:p|SUB|V|193|E;HGVS:p.V193E;VariantGroup:21;CorrespondingGene:2706 | p.A194T;tmVar:p|SUB|A|194|T;HGVS:p.A194T;VariantGroup:18;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
Four genes (including @GENE$, @GENE$, SCAP, TCF4) were found to be related to the PMI related. It turned out to be that only SCAP-c.3035C>T (@VARIANT$) and AGXT2-c.1103C>T (@VARIANT$) were predicted to be causive by both strategies. | 5,725,008 | AGXT2;12887 | ZFHX3;21366 | p.Ala1012Val;tmVar:p|SUB|A|1012|V;HGVS:p.A1012V;VariantGroup:2;CorrespondingGene:22937 | p.Ala338Val;tmVar:p|SUB|A|338|V;HGVS:p.A338V;VariantGroup:5;CorrespondingGene:64902 | 0no label |
In the subject III.1, the variant, carried in the heterozygous status, is the c.868 G > T; @VARIANT$, in the @GENE$ (CGK) gene; the III.2 subject carried the c.872 C > G; @VARIANT$, in the @GENE$ gene. | 8,306,687 | glucokinase;55440 | HNF1A;459 | p.Glu290*;tmVar:p|SUB|E|290|*;HGVS:p.E290*;VariantGroup:9;CorrespondingGene:2645 | p.Pro291Arg;tmVar:p|SUB|P|291|R;HGVS:p.P291R;VariantGroup:2;CorrespondingGene:6927;RS#:193922606;CA#:214336 | 0no label |
In patient AVM028, one novel heterozygous VUS (c.2207A>G [@VARIANT$]) in @GENE$ inherited from the father and one likely pathogenic de novo novel heterozygous variant (c.311T>C [@VARIANT$]) in TIMP3 were identified (online supplementary table S2). While TIMP3 blocks VEGF/@GENE$ signalling, RASA1 modulates differentiati... | 6,161,649 | RASA1;2168 | VEGFR2;55639 | p.His736Arg;tmVar:p|SUB|H|736|R;HGVS:p.H736R;VariantGroup:6;CorrespondingGene:5921;RS#:1403332745 | p.Leu104Pro;tmVar:p|SUB|L|104|P;HGVS:p.L104P;VariantGroup:7;CorrespondingGene:23592;RS#:1290872293 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/KAL1 (c.757G>A; p.Ala253Thr of NELF and c.488_490delGTT; @VARIANT$ of @GENE$) and @GENE$/TACR3 (c. 1160-13C>T of NELF and c.824G>A; @VARIANT$ of TACR3). | 3,888,818 | KAL1;55445 | NELF;10648 | p.Cys163del;tmVar:p|DEL|163|C;HGVS:p.163delC;VariantGroup:10;CorrespondingGene:3730 | p.Trp275X;tmVar:p|SUB|W|275|X;HGVS:p.W275X;VariantGroup:1;CorrespondingGene:6870;RS#:144292455;CA#:144871 | 0no label |
To the best of our knowledge, two of the identified variants (FOXC2: c.1183C>A, p.(H395N); and @GENE$: @VARIANT$, p.(P179T)) have not been previously identified. Examination of the genotype-phenotype correlation in this group suggests that the presence of the infrequent PITX2 variants increase the severity of the pheno... | 6,338,360 | PITX2;55454 | FOXC2;21091 | c.535C>A;tmVar:c|SUB|C|535|A;HGVS:c.535C>A;VariantGroup:3;CorrespondingGene:1545;RS#:771076928 | p.(H395N);tmVar:p|SUB|H|395|N;HGVS:p.H395N;VariantGroup:8;CorrespondingGene:2303 | 0no label |
To sum up, SH166-367, SH170-377, and SB175-334 which would have been considered DFNB1 without TES were found to be DFNB7/11, DFNB3, and @GENE$, respectively. Finally, a subject with the heterozygous @VARIANT$ mutation in @GENE$ (SH60-136) carried a @VARIANT$ variant in Wolfram syndrome 1 (WFS1) (NM_001145853) accordin... | 4,998,745 | DFNB16;15401 | GJB2;2975 | p.R143W;tmVar:p|SUB|R|143|W;HGVS:p.R143W;VariantGroup:1;CorrespondingGene:2706;RS#:80338948;CA#:172234 | p.D771N;tmVar:p|SUB|D|771|N;HGVS:p.D771N;VariantGroup:13;CorrespondingGene:7466;RS#:534067035;CA#:2839681 | 0no label |
CSS170323 carries a heterozygous missense variant @VARIANT$(p.Met210Ile) in MYOD1 and a heterozygous missense variant c.190G>A(@VARIANT$) in MEOX1 (Table 2). CSS170323 presented with L2 hemivertebra and fused ribs (the right 11th rib and 12th rib). During mesoderm development, the expression of MEOX1 is increased b... | 7,549,550 | MYOD1;7857 | TBX6;3389 | c.630G>C;tmVar:c|SUB|G|630|C;HGVS:c.630G>C;VariantGroup:9;CorrespondingGene:4654;RS#:749634841;CA#:5906491 | p.Ala64Thr;tmVar:p|SUB|A|64|T;HGVS:p.A64T;VariantGroup:5;CorrespondingGene:4222;RS#:373680176;CA#:8592682 | 0no label |
Patient P0432 has a c.4030_4037delATGGCTGG (p.M1344fsX42) mutation in @GENE$ and a missense mutation in @GENE$ (@VARIANT$), but his father, who has neither deafness nor retinitis pigmentosa, also carries these two mutations, and his clinically affected sister does not carry the mutation in CDH23. In the USH1 patient, w... | 3,125,325 | USH2A;66151 | CDH23;11142 | p.R1189W;tmVar:p|SUB|R|1189|W;HGVS:p.R1189W;VariantGroup:61;CorrespondingGene:64072;RS#:745855338;CA#:5544764 | c.46C>G;tmVar:c|SUB|C|46|G;HGVS:c.46C>G;VariantGroup:18;CorrespondingGene:124590;RS#:876657419;CA#:10576353 | 0no label |
The ISG20L2 and @GENE$ variants were excluded based on their frequencies in normal population cohorts. Sanger sequencing of Family 1 showed that both rs138355706 in @GENE$ (@VARIANT$, missense causing a p.R77C mutation) and a 4 bp deletion in S100A13 (@VARIANT$ causing a frameshift p.I80Gfs*13) segregated completely wi... | 6,637,284 | SETDB1;32157 | S100A3;2223 | c.229C>T;tmVar:c|SUB|C|229|T;HGVS:c.229C>T;VariantGroup:3;CorrespondingGene:6274;RS#:138355706;CA#:1116284 | c.238-241delATTG;tmVar:c|DEL|238_241|ATTG;HGVS:c.238_241delATTG;VariantGroup:13;CorrespondingGene:6284 | 0no label |
Recently, Gifford et al., identified three missense variants in @GENE$ (@VARIANT$), MYH7 (Leu387Phe), and @GENE$ (@VARIANT$) in three offspring with childhood-onset cardiomyopathy (Gifford et al., 2019). | 7,057,083 | MKL2;40917 | NKX2-5;1482;4824 | Gln670His;tmVar:p|SUB|Q|670|H;HGVS:p.Q670H;VariantGroup:2;CorrespondingGene:57496 | Ala119Ser;tmVar:p|SUB|A|119|S;HGVS:p.A119S;VariantGroup:0;CorrespondingGene:1482;RS#:137852684;CA#:120058 | 11 |
In AS patient IID27, the two mutations in COL4A5 and @GENE$ were inherited independently, likely indicating an in trans configuration. There is a splicing site mutation @VARIANT$ in @GENE$, inherited from her mother and a missense mutation @VARIANT$ (p. (Thr1474Met)) inherited from her father (Figure 1a). | 6,565,573 | COL4A4;20071 | COL4A5;133559 | c.1339 + 3A>T;tmVar:c|SUB|A|1339+3|T;HGVS:c.1339+3A>T;VariantGroup:23;CorrespondingGene:1287 | c.4421C > T;tmVar:c|SUB|C|4421|T;HGVS:c.4421C>T;VariantGroup:14;CorrespondingGene:1286;RS#:201615111;CA#:2144174 | 0no label |
The R171 and @VARIANT$ residues are in yellow. The 3D structure of EDA is shown in Figure 4. The G257 residue is located at the interface of two trimers. When G257R mutation happened, the side chain volume significantly enlarged, making it possible to form interaction with the R289 in adjacent trimer and abolish the st... | 3,842,385 | EDA;1896 | WNT10A;22525 | G213;tmVar:c|Allele|G|213;VariantGroup:4;CorrespondingGene:80326;RS#:147680216 | I312;tmVar:p|Allele|I|312;VariantGroup:7;CorrespondingGene:1896 | 0no label |
CVID, common variable immunodeficiency disorder; SLE, systemic lupus erythematosus; sIgAD, selective IgA deficiency; T1D, Type 1 Diabetes, sHGUS, symptomatic hypogammglobulinaemia of uncertain significance; WT, wild-type. (b) Electropherograms showing the T168fsX191 mutation of TCF3 and @VARIANT$ (c.310T>C) mutation of... | 5,671,988 | TACI;49320 | TCF3;2408 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | 0no label |
The detected @VARIANT$ variant affects the nuclear localization signal 2 (amino acids 568-574) of the @GENE$ protein. A previously characterized pathogenic nonsense variant (G1177X) and a rare missense alteration (@VARIANT$) were detected in the ALS2 gene, both in heterozygous form. The alsin protein encoded by the... | 6,707,335 | CCNF;1335 | ALS2;23264 | R572W;tmVar:p|SUB|R|572|W;HGVS:p.R572W;VariantGroup:25;CorrespondingGene:899;RS#:199743115;CA#:7842683 | R1499H;tmVar:p|SUB|R|1499|H;HGVS:p.R1499H;VariantGroup:4;CorrespondingGene:57679;RS#:566436589;CA#:2057559 | 0no label |
The proband in family PCG-139 also carried a rare PITX2 variant (@VARIANT$) and presented glaucoma diagnosed at the age of seven days. Both probands required more surgical operations to control IOP than the rest of patients. Below symbols are indicated genotypes for CYP1B1 and PITX2, age at diagnosis and number or surg... | 6,338,360 | FOXC2;21091 | PITX2;55454 | p.(A188T);tmVar:p|SUB|A|188|T;HGVS:p.A188T;VariantGroup:5;CorrespondingGene:5308;RS#:77144743;CA#:203139 | p.(P179T);tmVar:p|SUB|P|179|T;HGVS:p.P179T;VariantGroup:3;CorrespondingGene:1545;RS#:771076928 | 0no label |
Both homozygous and compound heterozygous variants in the @GENE$ gene have been described as causative for juvenile ALS. The @VARIANT$ nonsense variant was first detected in compound heterozygous form in a family with two affected siblings suffering from infantile ascending spastic paralysis with bulbar involvement. Th... | 6,707,335 | ALS2;23264 | MATR3;7830 | G1177X;tmVar:p|SUB|G|1177|X;HGVS:p.G1177X;VariantGroup:0;CorrespondingGene:57679;RS#:386134180;CA#:356568 | P11S;tmVar:p|SUB|P|11|S;HGVS:p.P11S;VariantGroup:6;RS#:995345187 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, @GENE$, PAX3, SOX10, SNAI2, and @GENE$) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; p.Arg203Cys) and TYRO3 (c.10... | 7,877,624 | MITF;4892 | TYRO3;4585 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
In this study, we performed whole-genome sequencing in 104 pathologically confirmed FTLD-TDP patients from the Mayo Clinic brain bank negative for @GENE$ and @GENE$ mutations and report on the contribution of rare single nucleotide and copy-number variants in 21 known neurodegenerative disease genes. Interestingly, we ... | 4,470,809 | C9ORF72;10137 | GRN;1577 | p.Q235*;tmVar:p|SUB|Q|235|*;HGVS:p.Q235*;VariantGroup:26;CorrespondingGene:29110 | p.A481V;tmVar:p|SUB|A|481|V;HGVS:p.A481V;VariantGroup:1;CorrespondingGene:10133;RS#:377219791;CA#:5410970 | 0no label |
The novel truncated variant in @GENE$ was not found in our "in-house" Saudi exome data (unpublished data from the Saudi Human Genome Project), 1000 Genome and gnomAD databases. The @VARIANT$ (p.R77C) variant in @GENE$ and @VARIANT$ (p.I80Gfs*13) mutation in S100A13 also segregated fully with ILD in Families 1B and 2. | 6,637,284 | S100A13;7523 | S100A3;2223 | c.229C>T;tmVar:c|SUB|C|229|T;HGVS:c.229C>T;VariantGroup:3;CorrespondingGene:6274;RS#:138355706;CA#:1116284 | c.238-241delATTG;tmVar:c|DEL|238_241|ATTG;HGVS:c.238_241delATTG;VariantGroup:13;CorrespondingGene:6284 | 0no label |
We observed that in 5 PCG cases heterozygous CYP1B1 mutations (p.A115P, p.E229 K, and @VARIANT$) co-occurred with heterozygous TEK mutations (@VARIANT$, p.I148T, p.Q214P, and p.G743A) indicating a potential digenic inheritance (Fig. 1a). None of the normal controls carried both the heterozygous combinations of @GENE$ a... | 5,953,556 | CYP1B1;68035 | TEK;397 | p.R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | p.E103D;tmVar:p|SUB|E|103|D;HGVS:p.E103D;VariantGroup:2;CorrespondingGene:7010;RS#:572527340;CA#:5015873 | 0no label |
Three rare missense variants (@VARIANT$, L2118V, and E2003D) of the SPG11 gene were found. The high detection rate of missense variants of this gene is probably due to the large size of the coding region; therefore, we suggest that these SPG11 variants are unlikely to be deleterious. Variants in the @GENE$ ... | 6,707,335 | SPG11;41614 | UBQLN2;81830 | R2034Q;tmVar:p|SUB|R|2034|Q;HGVS:p.R2034Q;VariantGroup:26;CorrespondingGene:80208;RS#:750101301;CA#:7534261 | Q84H;tmVar:p|SUB|Q|84|H;HGVS:p.Q84H;VariantGroup:43;CorrespondingGene:29978 | 0no label |
DFNB1 = nonsyndromic hearing loss and deafness 1, GJB2 = @GENE$, GJB3 = gap junction protein beta 3, GJB6 = gap junction protein beta 6, @GENE$ = microphthalmia-associated transcription factor. By screening other gap junction genes, another subject (SH175-389) carrying a single heterozygous @VARIANT... | 4,998,745 | gap junction protein beta 2;2975 | MITF;4892 | p.V193E;tmVar:p|SUB|V|193|E;HGVS:p.V193E;VariantGroup:21;CorrespondingGene:2706 | p.A194T;tmVar:p|SUB|A|194|T;HGVS:p.A194T;VariantGroup:18;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
Only 9 mutations previously reported as recurrent were detected in our series of patients (i.e. 11% of the mutations), specifically, c.1996C>T, c.223delG, c.1556G>A, c.494C>T, @VARIANT$ and c.5749G>T in @GENE$, c.238_239dupC in USH1C, and @VARIANT$ and c.10712C>T in @GENE$. Therefore, in the process of designing any st... | 3,125,325 | MYO7A;219 | USH2A;66151 | c.3719G>A;tmVar:c|SUB|G|3719|A;HGVS:c.3719G>A;VariantGroup:87;CorrespondingGene:4647;RS#:542400234;CA#:5545997 | c.2299delG;tmVar:c|DEL|2299|G;HGVS:c.2299delG;VariantGroup:190;CorrespondingGene:7399;RS#:80338903 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the @GENE$ gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and @GENE$ (c.1037T... | 7,877,624 | MITF;4892 | TYRO3;4585 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;CorrespondingGene:4286 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
@GENE$ Single Heterozygotes where DFNB1 was Excluded as a Final Molecular Diagnosis: A Fortuitously Detected GJB2 Mutation (Group I) There were three subjects (SH166-367, SH170-377, and SB175-334) with two recessive mutations, presumed to be pathogenic, in completely different deafness genes. One of the children with a... | 4,998,745 | GJB2;2975 | Transmembrane channel-like 1;23670 | c.235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:10;CorrespondingGene:2706;RS#:80338943 | p.W482R;tmVar:p|SUB|W|482|R;HGVS:p.W482R;VariantGroup:0;CorrespondingGene:117531;RS#:754142954;CA#:5081956 | 11 |
Surprisingly, we identified two missense mutations in the proband: NM_001257180.2, exon10, c.1787A>G, @VARIANT$ in @GENE$ (Figure 1c) and NM_002609.4, exon3, c.317G>C, p.Arg106Pro, @VARIANT$ in @GENE$ (Figure 1d). | 8,172,206 | SLC20A2;68531 | PDGFRB;1960 | p.His596Arg;tmVar:p|SUB|H|596|R;HGVS:p.H596R;VariantGroup:2;CorrespondingGene:6575 | rs544478083;tmVar:rs544478083;VariantGroup:1;CorrespondingGene:5159;RS#:544478083 | 11 |
Moreover, a heterozygous p.Gly213Ser (@VARIANT$) mutation was detected in exon 3 of WNT10A, this leads to the substitution of Gly at residue 213 to Ser. Sequence analyses revealed that both mutant alleles were from his mother (Fig. 2D), who had a very mild phenotype of isolated tooth agenesis. His father did not have m... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.637G>A;tmVar:c|SUB|G|637|A;HGVS:c.637G>A;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | c.466C>T;tmVar:c|SUB|C|466|T;HGVS:c.466C>T;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | 0no label |
Mutations in @GENE$ and @GENE$ in a patient with early-onset epileptic encephalopathy and respiratory depression Early infantile epileptic encephalopathy (EIEE) is a severe disorder associated with epilepsy, developmental delay and intellectual disability, and in some cases premature mortality. We report the case of a ... | 6,371,743 | NRXN1;21005 | NRXN2;86984 | c.2686C>T;tmVar:c|SUB|C|2686|T;HGVS:c.2686C>T;VariantGroup:1;CorrespondingGene:55777;RS#:796052777;CA#:316143 | p.Arg1059Gln;tmVar:p|SUB|R|1059|Q;HGVS:p.R1059Q;VariantGroup:2;CorrespondingGene:9379;RS#:777033569;CA#:6078001 | 11 |
c, d) Sequence chromatograms indicating the wild-type, homozygous affected and heterozygous carrier forms of c) the C to T transition at position c.229 changing the arginine residue to cysteine at position 77 of the @GENE$ protein (@VARIANT$; p.R77C) and d) the @VARIANT$ (p.I80Gfs*13) in @GENE$. Mutation name is based ... | 6,637,284 | S100A3;2223 | S100A13;7523 | c.229C>T;tmVar:c|SUB|C|229|T;HGVS:c.229C>T;VariantGroup:3;CorrespondingGene:6274;RS#:138355706;CA#:1116284 | c.238-241delATTG;tmVar:c|DEL|238_241|ATTG;HGVS:c.238_241delATTG;VariantGroup:13;CorrespondingGene:6284 | 11 |
CSS170323 carries a heterozygous missense variant c.630G>C(@VARIANT$) in MYOD1 and a heterozygous missense variant @VARIANT$(p.Ala64Thr) in @GENE$ (Table 2). CSS170323 presented with L2 hemivertebra and fused ribs (the right 11th rib and 12th rib). During mesoderm development, the expression of MEOX1 is increased b... | 7,549,550 | MEOX1;3326 | CS;56073 | p.Met210Ile;tmVar:p|SUB|M|210|I;HGVS:p.M210I;VariantGroup:9;CorrespondingGene:4654;RS#:749634841;CA#:5906491 | c.190G>A;tmVar:c|SUB|G|190|A;HGVS:c.190G>A;VariantGroup:5;CorrespondingGene:4222;RS#:373680176;CA#:8592682 | 0no label |
In patient AVM359, one heterozygous VUS (c.589C>T [@VARIANT$]) in @GENE$ inherited from the mother and one likely pathogenic de novo heterozygous variant (c.1592G>A [@VARIANT$]) in SCUBE2 were identified (online supplementary table S2). @GENE$ functions as a coreceptor that enhances VEGF/VEGFR2 binding to stimulate VEG... | 6,161,649 | ENG;92 | SCUBE2;36383 | p.Arg197Trp;tmVar:p|SUB|R|197|W;HGVS:p.R197W;VariantGroup:2;CorrespondingGene:2022;RS#:2229778 | p.Cys531Tyr;tmVar:p|SUB|C|531|Y;HGVS:p.C531Y;VariantGroup:5;CorrespondingGene:57758;RS#:1212415588 | 0no label |
Additionally, the monoallelic p.Gly213Ser (c.637G>A) mutation was also detected in exon 3 of @GENE$, it results in the substitution of Gly at residue 213 to Ser. Sequence analyses of her parents' genome revealed that the mutant alleles were from her mother (Fig. 2E), who only had microdontia of the upper lateral inciso... | 3,842,385 | WNT10A;22525 | EDA;1896 | p.Ala349Thr;tmVar:p|SUB|A|349|T;HGVS:p.A349T;VariantGroup:2;CorrespondingGene:1896;RS#:132630317;CA#:255657 | p.Arg171Cys;tmVar:p|SUB|R|171|C;HGVS:p.R171C;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
CONCLUSIONS We firstly identified the novel digenic heterozygous mutations by WES, @GENE$ p.307_308del and SCN5A p.R1865H, which resulted in LQTS with repeat syncope, torsades de pointes, ventricular fibrillation, and sinoatrial node dysfunction. KCNH2 p.307_308del may affect the functi... | 8,739,608 | KCNH2;201 | SCN5A;22738 | p.R1865H;tmVar:p|SUB|R|1865|H;HGVS:p.R1865H;VariantGroup:1;CorrespondingGene:6331;RS#:370694515;CA#:64651 | p.307_308del;tmVar:p|DEL|307_308|;HGVS:p.307_308del;VariantGroup:16;CorrespondingGene:3757 | 0no label |
Two potential disease-causing mutations were identified: (d) ENAM: @VARIANT$/ p.Asn197Ilefs*81, which was previously reported to cause ADAI in multiple families (Hart, Hart, et al., 2003; Kang et al., 2009; Kida et al., 2002; Pavlic et al., 2007; Wright et al., 2011). (e) @GENE$ missense mutation c.1559G>A/@VARIANT$. A... | 6,785,452 | LAMA3;18279 | ENAM;9698 | c.588+1delG;tmVar:c|DEL|588+1|G;HGVS:c.588+1delG;VariantGroup:9;CorrespondingGene:13801 | p.Cys520Tyr;tmVar:p|SUB|C|520|Y;HGVS:p.C520Y;VariantGroup:6;CorrespondingGene:3909 | 0no label |
Despite the absence of IgG detected in the supernatants of these cultures, no defect was observed in the generation of isotype switched IgG+ cells in II.2 (carrying both TNFRSF13B/@GENE$ @VARIANT$ and TCF3 @VARIANT$ mutations), compared to III.2, who has neither mutation. Her son, III.1, carrying the @GENE$ T168fsX191 ... | 5,671,988 | TACI;49320 | TCF3;2408 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (@VARIANT$) of the coding sequence in exon 7 of EDA, which results in the substitution of Gly at residue 257 to Arg. Additionally, the nucleotide sequence showed a monoallelic C to T transition at nucleotide 511 (c.511C>T) of the coding sequence in ex... | 3,842,385 | WNT10A;22525 | EDA;1896 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | Arg at residue 171 to Cys;tmVar:p|SUB|R|171|C;HGVS:p.R171C;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
A total of 2 novel variants, @VARIANT$ and @VARIANT$, were located in a myeloperoxidase-like domain, the catalytic site of the enzyme (Fig. S3B). A total of 4 TSHR variants were found in 2 patients and were compound heterozygotes for 2 different TSHR mutations. The @GENE$ variant p.R450H was a recurrent inactivating mu... | 7,248,516 | TSHR;315 | TRHR;20707 | p.S309P;tmVar:p|SUB|S|309|P;HGVS:p.S309P;VariantGroup:13;CorrespondingGene:2304;RS#:1162674885 | p.S571R;tmVar:p|SUB|S|571|R;HGVS:p.S571R;VariantGroup:26;CorrespondingGene:79048;RS#:765990605 | 0no label |
Notably, proband P05 in family 05 harbored a de novo @GENE$ c.1664-2A>C variant. Since the FGFR1 @VARIANT$ variant was evaluated as pathogenic according to the ACMG guideline, this family might be considered as a case of monogenic inheritance. However, proband P05 also carried a paternal variant (DCC @VARIANT$) and a m... | 8,152,424 | FGFR1;69065 | CCDC88C;18903 | c.1664-2A>C;tmVar:c|SUB|A|1664-2|C;HGVS:c.1664-2A>C;VariantGroup:25;CorrespondingGene:2260 | p. Gln91Arg;tmVar:p|SUB|Q|91|R;HGVS:p.Q91R;VariantGroup:1;CorrespondingGene:80067;RS#:766366919 | 0no label |
Variants in all known WS candidate genes (@GENE$, EDNRB, MITF, PAX3, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the @GENE$ gene in both patients. Moreover, heterozygous missense variants in SNAI3 (@VARIANT$; p.Arg203Cys) and TYRO3 (c.... | 7,877,624 | EDN3;88 | MITF;4892 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.607C>T;tmVar:c|SUB|C|607|T;HGVS:c.607C>T;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
M1, CYP1B1: @VARIANT$. M2, @GENE$: p.(E387K). M3, CYP1B1: p.(E173*). M4, PITX2: p.(P179T). M5, @GENE$: @VARIANT$. Arrows show the index cases. | 6,338,360 | CYP1B1;68035 | PITX2;55454 | p.(A179fs*18);tmVar:p|FS|A|179||18;HGVS:p.A179fsX18;VariantGroup:3;CorrespondingGene:1545;RS#:771076928 | p.(A188T);tmVar:p|SUB|A|188|T;HGVS:p.A188T;VariantGroup:5;CorrespondingGene:5308;RS#:77144743;CA#:203139 | 0no label |
The novel Q84H variant affects the N-terminal ubiquitin-like domain of the @GENE$ protein, which is involved in binding to proteasome subunits. FUS variants have been mostly detected in familial ALS cases that are localized within the C-terminus of the FUS protein. However, the two rare FUS variants (Y25C and P106L) t... | 6,707,335 | ubiquilin-2;81830 | TBK1;22742 | I397T;tmVar:p|SUB|I|397|T;HGVS:p.I397T;VariantGroup:11;CorrespondingGene:29110;RS#:755069538;CA#:6669001 | R261H;tmVar:p|SUB|R|261|H;HGVS:p.R261H;VariantGroup:2;CorrespondingGene:4750;RS#:200161705;CA#:203762 | 0no label |
These results were confirmed for the His24Leu and @VARIANT$ variants when using the reporters for CYP11A1 and HSD17B3 (Figure 2B,C). In contrast, variant @VARIANT$ did not change the reporter activities of CYP11A1 and @GENE$ (Figure 2B,C). Expression of NR5A1 variants was assessed by Western blot in our cell model. As ... | 7,696,449 | HSD17B3;20089 | AMH;68060 | Cys30Ser;tmVar:p|SUB|C|30|S;HGVS:p.C30S;VariantGroup:5;CorrespondingGene:6662;RS#:1003847603;CA#:293780979 | Cys301Tyr;tmVar:p|SUB|C|301|Y;HGVS:p.C301Y;VariantGroup:2;CorrespondingGene:6736 | 0no label |
Interestingly, one FALS proband carried 3 variants, each of which has previously been reported as pathogenic: SOD1 p.G38R, @GENE$ p.P136L, and @GENE$ @VARIANT$. Nine apparently sporadic subjects had variants in multiple genes (Table 4), but only two were well-established ALS mutations: TARDBP p.G287S was found in combi... | 4,293,318 | ANG;74385 | DCTN1;3011 | p.T1249I;tmVar:p|SUB|T|1249|I;HGVS:p.T1249I;VariantGroup:53;CorrespondingGene:1639;RS#:72466496;CA#:119583 | p.M170I;tmVar:p|SUB|M|170|I;HGVS:p.M170I;VariantGroup:45;CorrespondingGene:9217;RS#:143144050;CA#:9924276 | 0no label |
Moreover, the presence of other variants (KCNQ1-@VARIANT$, KCNH2-@VARIANT$, and KCNE1-p.G38S) could further enhance the effects of the mutant channels, thus resulting in incomplete penetrance and variable expressivity of the phenotype. On the contrary, in the mother, some other factors, including unknown genetic modifi... | 5,578,023 | KCNH2;201 | NOS1AP;136252 | p.R583H;tmVar:p|SUB|R|583|H;HGVS:p.R583H;VariantGroup:4;CorrespondingGene:3784;RS#:199473482;CA#:6304 | p.K897T;tmVar:p|SUB|K|897|T;HGVS:p.K897T;VariantGroup:0;CorrespondingGene:3757;RS#:1805123;CA#:7162 | 0no label |
Most had C9orf72 repeat expansion combined with another mutation (e.g. @GENE$ @VARIANT$ or @GENE$ A321V; Supplementary Table 6). A single control also had two mutations, P372R in ALS2 and @VARIANT$ in TARDBP. | 5,445,258 | VCP;5168 | TARDBP;7221 | R155H;tmVar:p|SUB|R|155|H;HGVS:p.R155H;VariantGroup:10;CorrespondingGene:7415;RS#:121909329;CA#:128983 | A90V;tmVar:p|SUB|A|90|V;HGVS:p.A90V;VariantGroup:40;CorrespondingGene:23435;RS#:80356715;CA#:586343 | 0no label |
Sequence alterations were detected in the COL6A3 (rs144651558), RYR1 (@VARIANT$), @GENE$ (rs138172448), and DES (@VARIANT$) genes. These variants were then screened in his sister who had inherited all variants except that found in the CAPN3 gene. The COL6A3 and @GENE$ variants were predicted to be benign by SIFT and Po... | 6,180,278 | CAPN3;52 | RYR1;68069 | rs143445685;tmVar:rs143445685;VariantGroup:1;CorrespondingGene:6261;RS#:143445685 | rs144901249;tmVar:rs144901249;VariantGroup:3;CorrespondingGene:1674;RS#:144901249 | 0no label |
In addition, we have confirmed that immunoreactive signal corresponding to the anti-ephrin-B2 antibody was colocalized with that to the anti-@GENE$ antibody in the inner ear (Supplementary Fig. 3g). These results suggest an important role of ephrin-B2 as an inducer of EphA2 endocytosis with the transmembrane binding pa... | 7,067,772 | EphA2;20929 | pendrin;20132 | S166N;tmVar:p|SUB|S|166|N;HGVS:p.S166N;VariantGroup:22;CorrespondingGene:23985 | F355L;tmVar:p|SUB|F|355|L;HGVS:p.F355L;VariantGroup:4;CorrespondingGene:1969;RS#:370923409 | 0no label |
Causative heterozygous mutations in @GENE$ (@VARIANT$/c.1145A > G) and @GENE$ (p.I1176L/c.3526A > C) were identified by whole exome sequencing performed on III-1 and IV-1. Sanger sequencing on available samples from consenting individuals was used for segregation analysis and confirmation of variants in individuals den... | 7,026,993 | GFI1;3854 | MYO6;56417 | p.N382S;tmVar:p|SUB|N|382|S;HGVS:p.N382S;VariantGroup:1;CorrespondingGene:2672;RS#:28936381;CA#:119872 | I1176L;tmVar:p|SUB|I|1176|L;HGVS:p.I1176L;VariantGroup:2;CorrespondingGene:4646;RS#:755922465;CA#:141060203 | 0no label |
DFNB1 = nonsyndromic hearing loss and deafness 1, GJB2 = @GENE$, GJB3 = @GENE$, GJB6 = gap junction protein beta 6, MITF = microphthalmia-associated transcription factor. By screening other gap junction genes, another subject (SH175-389) carrying a single heterozygous @VARIANT$ in GJB2 allele harbor... | 4,998,745 | gap junction protein beta 2;2975 | gap junction protein beta 3;7338 | p.V193E;tmVar:p|SUB|V|193|E;HGVS:p.V193E;VariantGroup:21;CorrespondingGene:2706 | p.A194T;tmVar:p|SUB|A|194|T;HGVS:p.A194T;VariantGroup:18;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
Subsequently, genetic testing for the LQT1, LQT2, LQT3, LQT5, and @GENE$ genes identified a heterozygous @VARIANT$ (@VARIANT$) mutation of the @GENE$ gene (LQT2) and a heterozygous c.170T > C (p.Ile57Thr) unclassified variant (UV) of the KCNE2 gene (LQT6). | 6,610,752 | LQT6;71688 | KCNH2;201 | c.3092_3096dup;tmVar:c|DUP|3092_3096||;HGVS:c.3092_3096dup;VariantGroup:2;CorrespondingGene:9992 | p.Arg1033ValfsX26;tmVar:p|FS|R|1033|V|26;HGVS:p.R1033VfsX26;VariantGroup:1;CorrespondingGene:3757 | 0no label |
In this family, the @GENE$/TACI @VARIANT$ mutation appears to demonstrate a gene dosage effect on serum IgG levels. The brother who is homozygous (II.4) for the TNFRSF13B/TACI C104R mutation has the lowest IgG levels, and consistently generated fewer isotype switched and differentiated ASC in vitro, compared with other... | 5,671,988 | TNFRSF13B;49320 | TCF3;2408 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | 11 |
Importantly, he had no coexistent mutations in CHD7, FGF8, FGFR1, PROK2, PROKR2, TAC3, TACR3, @GENE$, GNRHR, @GENE$, or KISS1R. The second patient (KS male C7) had a heterozygous c.757G>A (p.Ala253Thr) mutation (Figure 1; Table 1) affecting a completely conserved Ala253 residue (Figures S1-4). Using multiple sequence a... | 3,888,818 | KAL1;55445 | GNRH1;641 | p.Ala253Thr;tmVar:p|SUB|A|253|T;HGVS:p.A253T;VariantGroup:3;CorrespondingGene:26012;RS#:142726563;CA#:5370407 | p.Cys163del;tmVar:p|DEL|163|C;HGVS:p.163delC;VariantGroup:10;CorrespondingGene:3730 | 0no label |
Amino acid conservation analysis showed that seven of the 10 variants (@GENE$ p.G1122S, CELSR1 p.R769W, DVL3 p.R148Q, PTK7 p.P642R, SCRIB p.G1108E, SCRIB @VARIANT$ and @GENE$ @VARIANT$) were located at highly conserved nucleotides in human, dog, mouse, rat, and zebrafish. | 5,966,321 | CELSR1;7665 | SCRIB;44228 | p.G644V;tmVar:p|SUB|G|644|V;HGVS:p.G644V;VariantGroup:9;CorrespondingGene:23513;RS#:201104891;CA#:187609256 | p.K618R;tmVar:p|SUB|K|618|R;HGVS:p.K618R;VariantGroup:2;CorrespondingGene:5754;RS#:139041676 | 0no label |
We identified a novel compound heterozygous variant in @GENE$ c.1285dup (p.(Arg429Profs*72); a likely pathogenic novel variant affecting the conserved residue 354 in the functional domain of @GENE$ (c.1062C > G; p.(Asn354Lys)); a pathogenic new homozygous nucleotide change in BBS7 that leads to a @VARIANT$, c.763A > T,... | 6,567,512 | BBS1;11641 | BBS2;12122 | stop codon in position 255;tmVar:p|Allele|X|255;VariantGroup:1;CorrespondingGene:79738;RS#:139658279 | c.1235G > T;tmVar:c|SUB|G|1235|T;HGVS:c.1235G>T;VariantGroup:15;CorrespondingGene:8195;RS#:1396840386 | 0no label |
Variants in all known WS candidate genes (@GENE$, EDNRB, MITF, @GENE$, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and TYRO3 (c.1037... | 7,877,624 | EDN3;88 | PAX3;22494 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;CorrespondingGene:4286 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
These data also indicate that an alternate pathway is used for quality control of pro-@GENE$ when MAN1B1 alpha-mannosidase activity is reduced. DISCUSSION In this study, we describe identification and characterization of abnormalities in patients with homozygous mutations in two genes, a novel mutation in SEC23A, @VARI... | 4,853,519 | COL1A1;73874 | MAN1B1;5230 | 1200G>C;tmVar:c|SUB|G|1200|C;HGVS:c.1200G>C;VariantGroup:0;CorrespondingGene:10484;RS#:866845715;CA#:259543384 | 1000C>T;tmVar:c|SUB|C|1000|T;HGVS:c.1000C>T;VariantGroup:4;CorrespondingGene:11253;RS#:387906886;CA#:129197 | 0no label |
Two different GJB3 mutations (N166S and A194T) occurring in compound heterozygosity with the 235delC and 299delAT of GJB2 were identified in three unrelated families (@VARIANT$/@VARIANT$, 235delC/A194T and 299delAT/A194T). Neither of these mutations in Cx31 was detected in DNA from 200 unrelated Chinese controls. Direc... | 2,737,700 | Cx26;2975 | Cx31;7338 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | N166S;tmVar:p|SUB|N|166|S;HGVS:p.N166S;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 0no label |
Amino acid conservation analysis showed that seven of the 10 variants (CELSR1 p.G1122S, CELSR1 p.R769W, @GENE$ p.R148Q, PTK7 @VARIANT$, SCRIB @VARIANT$, SCRIB p.G644V and @GENE$ p.K618R) were located at highly conserved nucleotides in human, dog, mouse, rat, and zebrafish. | 5,966,321 | DVL3;20928 | SCRIB;44228 | p.P642R;tmVar:p|SUB|P|642|R;HGVS:p.P642R;VariantGroup:5;CorrespondingGene:5754;RS#:148120569;CA#:3816292 | p.G1108E;tmVar:p|SUB|G|1108|E;HGVS:p.G1108E;VariantGroup:3;CorrespondingGene:23513;RS#:529610993;CA#:4918763 | 0no label |
The p.Ile312Met (@VARIANT$) mutation in @GENE$ and heterozygous p.Arg171Cys (c.511C>T) mutation in WNT10A were detected. The coding sequence in exon 9 of EDA showed a C to G transition, which results in the substitution of @VARIANT$; also, the coding sequence in exon 3 of WNT10A showed a C to T transition at nucleotide... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.936C>G;tmVar:c|SUB|C|936|G;HGVS:c.936C>G;VariantGroup:1;CorrespondingGene:80326 | Ile at residue 312 to Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | 0no label |
The P11S variant affects the b isoform of the @GENE$ protein (NM_001194956 and NP_001181885), contributing to splicing alteration of other isoforms. Further evidence is required to elucidate the mechanism of pathogenicity of these alterations. We discovered several variants in ALS candidate and risk genes. In a patient... | 6,707,335 | MATR3;7830 | DYNC1H1;1053 | T2583I;tmVar:p|SUB|T|2583|I;HGVS:p.T2583I;VariantGroup:31;CorrespondingGene:1778 | H398R;tmVar:p|SUB|H|398|R;HGVS:p.H398R;VariantGroup:18;CorrespondingGene:2632;RS#:755004170;CA#:2499769 | 0no label |
Three variants of @GENE$ (NM_007123), @VARIANT$, C4870F, and G805A with unknown pathogenic potential were identified using TES (see Table S3, Supplemental Content, which illustrates variants or mutations of Usher syndrome type 2A (USH2A) and Ankyrin 1 (@GENE$) identified in SH 94-208). However, this subject showed no r... | 4,998,745 | USH2A;66151 | ANK1;55427 | R5143C;tmVar:p|SUB|R|5143|C;HGVS:p.R5143C;VariantGroup:6;CorrespondingGene:7399;RS#:145771342;CA#:182576 | G1748S;tmVar:p|SUB|G|1748|S;HGVS:p.G1748S;VariantGroup:19;CorrespondingGene:286;RS#:746486928;CA#:4727361 | 0no label |
Analysis of the entire coding region of the @GENE$ gene revealed the presence of two different missense mutations (N166S and A194T) occurring in compound heterozygosity along with the 235delC and 299delAT of @GENE$ in 3 simplex families (235delC/@VARIANT$, @VARIANT$/A194T and 299delAT/A194T). | 2,737,700 | Cx31;7338 | GJB2;2975 | N166S;tmVar:p|SUB|N|166|S;HGVS:p.N166S;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | 0no label |
A new pathogenic variant in BBS2 affecting a conserved residue in the functional domain of BBsome protein (c.1062C > G; @VARIANT$) was found in compound heterozygous state in patient #1 together with the known pathogenic variant p.(Arg339*). A new homozygous nucleotide change in BBS7 that leads to a stop codon in p... | 6,567,512 | BBS7;12395 | BBS6;10318 | p.(Asn354Lys);tmVar:p|SUB|N|354|K;HGVS:p.N354K;VariantGroup:23;CorrespondingGene:583 | Cys412Phe;tmVar:p|SUB|C|412|F;HGVS:p.C412F;VariantGroup:15;CorrespondingGene:8195;RS#:1396840386 | 0no label |
The nucleotide sequence showed a G to C transition at nucleotide 769 (@VARIANT$) of the coding sequence in exon 7 of @GENE$, which results in the substitution of Gly at residue 257 to Arg. Additionally, the nucleotide sequence showed a monoallelic C to T transition at nucleotide 511 (c.511C>T) of the coding sequence in... | 3,842,385 | EDA;1896 | WNT10A;22525 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | c.511C>T;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
We have screened 108 GJB2 heterozygous Chinese patients for mutations in @GENE$ by sequencing. We have excluded the possibility that mutations in exon 1 of @GENE$ and the deletion of GJB6 are the second mutant allele in these Chinese heterozygous probands. Two different GJB3 mutations (N166S and @VARIANT$) occurring in... | 2,737,700 | GJB3;7338 | GJB2;2975 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | 0no label |
Subsequently, genetic testing for the LQT1, LQT2, LQT3, LQT5, and LQT6 genes identified a heterozygous @VARIANT$ (@VARIANT$) mutation of the KCNH2 gene (LQT2) and a heterozygous c.170T > C (p.Ile57Thr) unclassified variant (UV) of the KCNE2 gene (LQT6). The UV (missense mutation) of the KCNE2 gene is likely a pathogeni... | 6,610,752 | LQT2;201 | LQT6;71688 | c.3092_3096dup;tmVar:c|DUP|3092_3096||;HGVS:c.3092_3096dup;VariantGroup:2;CorrespondingGene:9992 | p.Arg1033ValfsX26;tmVar:p|FS|R|1033|V|26;HGVS:p.R1033VfsX26;VariantGroup:1;CorrespondingGene:3757 | 0no label |
To investigate the effects of one candidate variant on mutant @GENE$ function, Western blotting and coimmunofluorescence were used to assess binding capacity, and leptomycin B exposure along with immunofluorescence was used to assess nuclear localization. Results: We describe a child who presented in infancy with combi... | 5,505,202 | WDR11;41229 | PROKR2;16368 | p.R85C;tmVar:p|SUB|R|85|C;HGVS:p.R85C;VariantGroup:1;CorrespondingGene:128674;RS#:74315418 | c.1306A>G;tmVar:c|SUB|A|1306|G;HGVS:c.1306A>G;VariantGroup:3;CorrespondingGene:55717;RS#:34602786;CA#:5719694 | 0no label |
Previous studies suggested that heterozygous variants in the @GENE$ may be causative for adult-onset sALS. @GENE$ encodes three protein isoforms that have been described as nuclear-matrix and DNA/RNA binding proteins involved in transcription and stabilization of mRNA. In the present study, two novel heterozygous vari... | 6,707,335 | ALS2;23264 | MATR3;7830 | S275N;tmVar:p|SUB|S|275|N;HGVS:p.S275N;VariantGroup:9;CorrespondingGene:80208;RS#:995711809 | G4290R;tmVar:p|SUB|G|4290|R;HGVS:p.G4290R;VariantGroup:27;CorrespondingGene:1778;RS#:748643448;CA#:7354051 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, @GENE$, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and @GENE$ (c.1037T... | 7,877,624 | SOX10;5055 | TYRO3;4585 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
The proband's son (III.1) has inherited the TCF3 T168fsX191 mutation, but not the TNFRSF13B/@GENE$ @VARIANT$ mutation. The proband's clinically unaffected daughter (III.2) has not inherited either mutation. The @GENE$ @VARIANT$ mutation was absent in the proband's parents, indicating a de novo origin. | 5,671,988 | TACI;49320 | TCF3;2408 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | 0no label |
In patient AVM226, we identified the compound heterozygous variants c.3775G>A (@VARIANT$) and @VARIANT$ (p.Gln989Leu) in @GENE$ (table 2). @GENE$ and DSCAM have similar neurodevelopmental functions and are essential for self-avoidance in the developing mouse retina. | 6,161,649 | DSCAM;74393 | DSCAML1;79549 | p.Val1259Ile;tmVar:p|SUB|V|1259|I;HGVS:p.V1259I;VariantGroup:5;CorrespondingGene:1826;RS#:1212415588 | c.2966A>T;tmVar:c|SUB|A|2966|T;HGVS:c.2966A>T;VariantGroup:5;CorrespondingGene:83394;RS#:1212415588 | 0no label |
While tagged versions of EphA2 @VARIANT$ and EphA2 T511M were effectively precipitated with Fc-fusion @GENE$ compared to EphA2 WT, Fc-fusion ephrin-B2 failed to pull down EphA2 G355R and T511M (Fig. 7a). Consistently, internalization of EphA2 G355R and EphA2 T511M with @GENE$ induced by ephrin-B2 but not ephrin-A1 was ... | 7,067,772 | ephrin-A1;3262 | pendrin;20132 | G355R;tmVar:p|SUB|G|355|R;HGVS:p.G355R;VariantGroup:4;CorrespondingGene:1969;RS#:370923409;CA#:625329 | H723R;tmVar:p|SUB|H|723|R;HGVS:p.H723R;VariantGroup:10;CorrespondingGene:5172;RS#:121908362;CA#:253307 | 0no label |
The DNA sequencing chromatograms from the proband show two @GENE$ and one @GENE$ heterozygous mutations. While both LRP6 variants, p.(@VARIANT$) and p.(Asn1075Ser), were inherited from her father, the WNT10A mutation, @VARIANT$ was maternally derived. | 8,621,929 | LRP6;1747 | WNT10A;22525 | Ser127Thr;tmVar:p|SUB|S|127|T;HGVS:p.S127T;VariantGroup:1;CorrespondingGene:4040;RS#:17848270;CA#:6455897 | p.(Glu167Gln);tmVar:p|SUB|E|167|Q;HGVS:p.E167Q;VariantGroup:5;CorrespondingGene:80326;RS#:148714379 | 11 |
Five anencephaly cases carried rare or novel CELSR1 missense variants, three of whom carried additional rare potentially damaging PCP variants: 01F377 (@GENE$ c.6362G>A and PRICKLE4 c.730C>G), 2F07 (CELSR1 c.8807C>T and DVL3 @VARIANT$), 618F05 (CELSR1 c.8282C>T and SCRIB @VARIANT$). One patient (f93-80) had a novel PTK... | 5,887,939 | CELSR1;7665 | CELSR2;1078 | c.1622C>T;tmVar:c|SUB|C|1622|T;HGVS:c.1622C>T;VariantGroup:5;CorrespondingGene:1857;RS#:1311053970 | c.3979G>A;tmVar:c|SUB|G|3979|A;HGVS:c.3979G>A;VariantGroup:31;CorrespondingGene:23513;RS#:201563528;CA#:4918429 | 0no label |
To investigate the role of GJB3 variations along with GJB2 mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous GJB2 mutations for variants in @GENE$ by sequencing. Analysis of the entire coding region of the Cx31 gene revealed the presence of two different misse... | 2,737,700 | Cx31;7338 | GJB2;2975 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | N166S;tmVar:p|SUB|N|166|S;HGVS:p.N166S;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 0no label |
The proband (arrow, II.2) is heterozygous for both the TCF3 @VARIANT$ and TNFRSF13B/@GENE$ C104R mutations. Other family members who have inherited @GENE$ T168fsX191 and TNFRSF13B/TACI @VARIANT$ mutations are shown. | 5,671,988 | TACI;49320 | TCF3;2408 | T168fsX191;tmVar:p|FS|T|168||191;HGVS:p.T168fsX191;VariantGroup:1;CorrespondingGene:6929 | C104R;tmVar:p|SUB|C|104|R;HGVS:p.C104R;VariantGroup:2;CorrespondingGene:23495;RS#:34557412;CA#:117387 | 0no label |
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