sentence stringlengths 61 1.36k | pmcid int32 162k 8.8M | gene1 stringclasses 381
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Notably, proband P05 in family 05 harbored a de novo FGFR1 @VARIANT$ variant. Since the @GENE$ c.1664-2A>C 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 p. Gln91Arg) and a... | 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. Arg1299Cys;tmVar:p|SUB|R|1299|C;HGVS:p.R1299C;VariantGroup:4;CorrespondingGene:440193;RS#:142539336;CA#:7309192 | 0no label |
On the other hand, mutant GFP-@GENE$ A115P and @VARIANT$ showed perturbed interaction with HA-@GENE$. The residues @VARIANT$, I148, and Q214 lie in the N-terminal extracellular domain of TEK (Fig. 1d). | 5,953,556 | CYP1B1;68035 | TEK;397 | R368H;tmVar:p|SUB|R|368|H;HGVS:p.R368H;VariantGroup:1;CorrespondingGene:1545;RS#:79204362;CA#:119016 | E103;tmVar:p|Allele|E|103;VariantGroup:2;CorrespondingGene:7010;RS#:572527340 | 0no label |
In Vitro Functional Studies of Novel GATA4 Variants To test the transcriptional activity of identified @GENE$ variants, we constructed mammalian expression vectors of wt and mutant GATA4 and tested them on three different promoters that have been described being regulated by GATA4, namely the AMH, SRY, and CYP17 promot... | 5,893,726 | GATA4;1551 | CYP17;73875 | Trp228Cys;tmVar:p|SUB|W|228|C;HGVS:p.W228C;VariantGroup:3;CorrespondingGene:4038 | Pro226Leu;tmVar:p|SUB|P|226|L;HGVS:p.P226L;VariantGroup:1;CorrespondingGene:2626;RS#:368991748 | 0no label |
The @VARIANT$ and R148P 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 GRN gene. Los... | 6,707,335 | GRN;1577 | SQSTM1;31202 | T338I;tmVar:p|SUB|T|338|I;HGVS:p.T338I;VariantGroup:5;CorrespondingGene:4744;RS#:774252076;CA#:10174087 | E389Q;tmVar:p|SUB|E|389|Q;HGVS:p.E389Q;VariantGroup:24;CorrespondingGene:8878;RS#:1391182750 | 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 (235delC/@VARIANT$, 235delC/A194T and @VARIANT$/A194T). Neither of these mutations in Cx31 was detected in DNA from 200 unrelated Chinese controls. Direct... | 2,737,700 | Cx26;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 |
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 GRN gene. Los... | 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 |
Our results indicate that the novel KCNH2-@VARIANT$ variant can be a pathogenic LQTS mutation, whereas @GENE$-p.R583H, @GENE$-p.K897T, and KCNE1-@VARIANT$ could be LQTS modifiers. | 5,578,023 | KCNQ1;85014 | KCNH2;201 | 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 | 0no label |
The coding sequence in exon 9 of @GENE$ showed a C to G transition, which results in the substitution of @VARIANT$; also, the coding sequence in exon 3 of @GENE$ showed a C to T transition at nucleotide 511, which results in the substitution of @VARIANT$. Analyses of his parents' genome revealed that the mutant alleles... | 3,842,385 | EDA;1896 | WNT10A;22525 | Ile at residue 312 to Met;tmVar:p|SUB|I|312|M;HGVS:p.I312M;VariantGroup:7;CorrespondingGene:1896 | Arg at residue 171 to Cys;tmVar:p|SUB|R|171|C;HGVS:p.R171C;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 11 |
None of 2,504 self-declared healthy individuals in TGP has both @GENE$, @VARIANT$ (p.Asn357Ser) and @GENE$, c.1175C > T (p.Pro392Leu). No other pathogenic or suspected pathogenic variants in genes associated with muscle diseases were identified in the proband of family 2 by expanded NGS panel studies or in the proband ... | 5,868,303 | TIA1;20692 | SQSTM1;31202 | c.1070A > G;tmVar:c|SUB|A|1070|G;HGVS:c.1070A>G;VariantGroup:5;CorrespondingGene:7072;RS#:116621885;CA#:1697407 | 179260153C/T;tmVar:c|SUB|C|179260153|T;HGVS:c.179260153C>T;VariantGroup:9;CorrespondingGene:8878;RS#:4935;CA#:3600710 | 0no label |
In the USH1 patient, we found three presumably pathogenic mutations in MYO7A (c.6657T>C), @GENE$ (@VARIANT$; p.L16V) and @GENE$ (@VARIANT$). | 3,125,325 | USH1G;56113 | USH2A;66151 | c.46C>G;tmVar:c|SUB|C|46|G;HGVS:c.46C>G;VariantGroup:18;CorrespondingGene:124590;RS#:876657419;CA#:10576353 | c.9921T>G;tmVar:c|SUB|T|9921|G;HGVS:c.9921T>G;VariantGroup:115;CorrespondingGene:7399;RS#:1057519382 | 11 |
WES demonstrated heterozygous missense mutations in two genes required for pituitary development, a known loss-of-function mutation in PROKR2 (@VARIANT$;p.R85C) inherited from an unaffected mother, and a @GENE$ (c.1306A>G;@VARIANT$) mutation inherited from an unaffected father. Mutant WDR11 loses its capacity to bind t... | 5,505,202 | WDR11;41229 | EMX1;55799 | c.253C>T;tmVar:c|SUB|C|253|T;HGVS:c.253C>T;VariantGroup:1;CorrespondingGene:128674;RS#:74315418;CA#:259601 | p.I436V;tmVar:p|SUB|I|436|V;HGVS:p.I436V;VariantGroup:3;CorrespondingGene:55717;RS#:34602786;CA#:5719694 | 0no label |
Proband 17 inherited CHD7 @VARIANT$ and CDON p. Val969Ile variants from his unaffected father and mother, respectively. Notably, proband P05 in family 05 harbored a de novo FGFR1 c.1664-2A>C variant. Since the FGFR1 c.1664-2A>C variant was evaluated as pathogenic according to the ACMG guideline, this family might be co... | 8,152,424 | DCC;21081 | CCDC88C;18903 | p. Trp1994Gly;tmVar:p|SUB|W|1994|G;HGVS:p.W1994G;VariantGroup:14;CorrespondingGene:55636 | p. Arg1299Cys;tmVar:p|SUB|R|1299|C;HGVS:p.R1299C;VariantGroup:4;CorrespondingGene:440193;RS#:142539336;CA#:7309192 | 0no label |
Three rare missense variants (R2034Q, L2118V, and @VARIANT$) of the SPG11 gene were found. The high detection rate of missense variants of this gene is probably due to the large size of the coding region; therefore, we suggest that these @GENE$ variants are unlikely to be deleterious. Variants in the SPG11 ... | 6,707,335 | SPG11;41614 | UBQLN2;81830 | E2003D;tmVar:p|SUB|E|2003|D;HGVS:p.E2003D;VariantGroup:3;CorrespondingGene:80208;RS#:954483795 | M392V;tmVar:p|SUB|M|392|V;HGVS:p.M392V;VariantGroup:17;CorrespondingGene:29978;RS#:104893941 | 0no label |
The substitutions of Leu117 to Phe (L117F), Ser166 to Asn (S166N), and @VARIANT$ (F335L), identified in Pendred syndrome patients, do not affect their membrane localization. Given the reported normal function of pendrin L117F and pendrin S166N as an anion exchanger, compromised regulatory machinery of pendrin functi... | 7,067,772 | pendrin;20132 | EphA2;20929 | Phe335 to Leu;tmVar:p|SUB|F|335|L;HGVS:p.F335L;VariantGroup:20;CorrespondingGene:13836 | F355L;tmVar:p|SUB|F|355|L;HGVS:p.F355L;VariantGroup:4;CorrespondingGene:1969;RS#:370923409 | 0no label |
In Family F, the GJB2/@VARIANT$ was inherited from the unaffected father and the A194T of GJB3 was likely inherited from the normal hearing deceased mother (Fig. 1f). In Family K, genotyping analysis revealed that the father transmitted the @VARIANT$/@GENE$, while the mother is heterozygous for the @GENE$/299-300delAT ... | 2,737,700 | GJB3;7338 | GJB2;2975 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
CVID, common variable immunodeficiency disorder; SLE, systemic lupus erythematosus; sIgAD, selective IgA deficiency; T1D, Type 1 Diabetes, sHGUS, symptomatic hypogammglobulinaemia of uncertain significance; WT, wild-type. (b) Electropherograms showing the @VARIANT$ mutation of TCF3 and @VARIANT$ (c.310T>C) mutation of ... | 5,671,988 | TNFRSF13B;49320 | AD1;56379 | 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 |
Variants in all known WS candidate genes (EDN3, @GENE$, MITF, @GENE$, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and TYRO3 (c.1037... | 7,877,624 | EDNRB;89 | PAX3;22494 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
The @VARIANT$ (p.His596Arg) mutation of @GENE$ has been reported in a 66-year-old patient with sporadic primary familial brain calcification who was also clinically asymptomatic (Guo et al., 2019). The c.317G>C (@VARIANT$) variant of @GENE$, a rare single nucleotide polymorphism (SNP, rs544478083), has not yet been sho... | 8,172,206 | SLC20A2;68531 | PDGFRB;1960 | c.1787A>G;tmVar:c|SUB|A|1787|G;HGVS:c.1787A>G;VariantGroup:2;CorrespondingGene:6575 | p.Arg106Pro;tmVar:p|SUB|R|106|P;HGVS:p.R106P;VariantGroup:1;CorrespondingGene:5159;RS#:544478083 | 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 |
Moreover, a heterozygous p.Gly213Ser (@VARIANT$) mutation was detected in exon 3 of @GENE$, 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 | WNT10A;22525 | EDA;1896 | c.637G>A;tmVar:c|SUB|G|637|A;HGVS:c.637G>A;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | p.Arg156Cys;tmVar:p|SUB|R|156|C;HGVS:p.R156C;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | 0no label |
The nucleotide sequence showed a T deletion at nucleotide 252 (c.252DelT) of the coding sequence in exon 1 of EDA; this leads to a frame shift from residue 84 and a premature @VARIANT$. Additionally, a monoallelic C to T transition at nucleotide 511 (@VARIANT$) of the coding sequence in exon 3 of WNT10A was detected, t... | 3,842,385 | EDA;1896 | WNT10A;22525 | termination at residue 90;tmVar:p|Allele|X|90;VariantGroup:10;CorrespondingGene:1896 | c.511C>T;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
In those samples, no mutation was detected on the second allele either in @GENE$-exon-1/splice sites or in GJB6. To investigate the role of @GENE$ variations along with GJB2 mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous GJB2 mutations for variants in Cx31 ... | 2,737,700 | Cx26;2975 | GJB3;7338 | 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 |
We report digenic variants in SCRIB and PTK7 associated with NTDs in addition to SCRIB and @GENE$ heterozygous variants in additional NTD cases. The combinatorial variation of PTK7 c.1925C > G (@VARIANT$) and @GENE$ c.3323G > A (@VARIANT$) only occurred in one spina bifida case, and was not found in the 1000G database ... | 5,966,321 | CELSR1;7665 | SCRIB;44228 | p.P642R;tmVar:p|SUB|P|642|R;HGVS:p.P642R;VariantGroup:5;CorrespondingGene:5754;RS#:148120569;CA#:3816292 | p.G1108E;tmVar:p|SUB|G|1108|E;HGVS:p.G1108E;VariantGroup:3;CorrespondingGene:23513;RS#:529610993;CA#:4918763 | 0no label |
On the other hand, two missense mutations of the EPHA2 gene were identified in two families, @GENE$: @VARIANT$ (p.434A>T), EPHA2: c.1063G>A (p.G355R) and SLC26A4: c.1229C>A (p.410T>M), @GENE$: @VARIANT$ (p.T511M) (Fig. 6a, b). | 7,067,772 | SLC26A4;20132 | EPHA2;20929 | c.1300G>A;tmVar:c|SUB|G|1300|A;HGVS:c.1300G>A;VariantGroup:1;CorrespondingGene:5172;RS#:757552791;CA#:4432772 | c.1532C>T;tmVar:c|SUB|C|1532|T;HGVS:c.1532C>T;VariantGroup:5;CorrespondingGene:1969;RS#:55747232;CA#:625151 | 0no label |
Variants in all known WS candidate genes (@GENE$, EDNRB, MITF, PAX3, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in @GENE$ (c.607C>T; @VARIANT$) and TYRO3 (c.1037... | 7,877,624 | EDN3;88 | SNAI3;8500 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
Since TTC26 is an intraflagellar transport (IFT) protein in cilia, we aimed to identify potential interactions between @GENE$ and TTC26. Using coimmunoprecipitation assays, we found that the myc-tagged mutant @VARIANT$ and p.R197C @GENE$ proteins pulled down the Flag-tagged mutant @VARIANT$ and p.R566L FLNB proteins, r... | 7,279,190 | FLNB;37480 | TTC26;11786 | p.R50C;tmVar:p|SUB|R|50|C;HGVS:p.R50C;VariantGroup:21;CorrespondingGene:79989;RS#:143880653;CA#:4508058 | p.A2282T;tmVar:p|SUB|A|2282|T;HGVS:p.A2282T;VariantGroup:6;CorrespondingGene:2317;RS#:1339176246 | 0no label |
We identified a novel compound heterozygous variant in BBS1 c.1285dup (p.(Arg429Profs*72); a likely pathogenic novel variant affecting the conserved residue 354 in the functional domain of @GENE$ (@VARIANT$; p.(Asn354Lys)); a pathogenic new homozygous nucleotide change in BBS7 that leads to a stop codon in position 255... | 6,567,512 | BBS2;12122 | BBS6;10318 | c.1062C > G;tmVar:c|SUB|C|1062|G;HGVS:c.1062C>G;VariantGroup:22;CorrespondingGene:583 | Cys412Phe;tmVar:p|SUB|C|412|F;HGVS:p.C412F;VariantGroup:15;CorrespondingGene:8195;RS#:1396840386 | 0no label |
Moreover, patients carrying a LAMA4 @VARIANT$ 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 | L1038P;tmVar:p|SUB|L|1038|P;HGVS:p.L1038P;VariantGroup:8;CorrespondingGene:4625;RS#:551897533;CA#:257817954 | 0no label |
Two different GJB3 mutations (N166S and A194T) occurring in compound heterozygosity with the 235delC and 299delAT of @GENE$ were identified in three unrelated families (235delC/N166S, 235delC/A194T and @VARIANT$/@VARIANT$). Neither of these mutations in @GENE$ was detected in DNA from 200 unrelated Chinese controls. | 2,737,700 | GJB2;2975 | Cx31;7338 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
(C) The sequence of the @VARIANT$ variant is well-conserved from humans to tunicates. (D) SH175-389 harbored a monoallelic p.V193E variant of GJB2 and a monoallelic @VARIANT$ variant of GJB3. DFNB1 = nonsyndromic hearing loss and deafness 1, GJB2 = gap junction protein beta 2, GJB3 = gap junction protein beta 3, @GENE$... | 4,998,745 | GJB6;4936 | MITF;4892 | p.R341C;tmVar:p|SUB|R|341|C;HGVS:p.R341C;VariantGroup:7;CorrespondingGene:161497;RS#:1359505251 | p.A194T;tmVar:p|SUB|A|194|T;HGVS:p.A194T;VariantGroup:18;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
Two different GJB3 mutations (@VARIANT$ and A194T) occurring in compound heterozygosity with the 235delC and 299delAT of GJB2 were identified in three unrelated families (235delC/N166S, @VARIANT$/A194T and 299delAT/A194T). Neither of these mutations in Cx31 was detected in DNA from 200 unrelated Chinese controls. Direc... | 2,737,700 | Cx26;2975 | Cx31;7338 | N166S;tmVar:p|SUB|N|166|S;HGVS:p.N166S;VariantGroup:0;CorrespondingGene:2707;RS#:121908851;CA#:118311 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | 0no label |
Results Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, @VARIANT$), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees. D... | 6,081,235 | HS1BP3;10980 | DNAH17;72102 | p.Pro2421Val;tmVar:p|SUB|P|2421|V;HGVS:p.P2421V;VariantGroup:3;CorrespondingGene:80346 | p.Gly32Cys;tmVar:p|SUB|G|32|C;HGVS:p.G32C;VariantGroup:25;CorrespondingGene:64342 | 0no label |
It turned out to be that only @GENE$-c.3035C>T (@VARIANT$) and @GENE$-c.1103C>T (@VARIANT$) were predicted to be causive by both strategies. | 5,725,008 | SCAP;8160 | AGXT2;12887 | 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 |
He is a carrier of @GENE$ (MIM 606463; GenBank: NM_001005741.2; rs7673715) @VARIANT$; p.N409S and @GENE$ (MIM 600509; NM_000352.4; @VARIANT$) c.3989-9G>A mutations. | 5,505,202 | GBA;68040 | ABCC8;68048 | c.1226A>G;tmVar:c|SUB|A|1226|G;HGVS:c.1226A>G;VariantGroup:7;CorrespondingGene:2629;RS#:76763715;CA#:116767 | rs151344623;tmVar:rs151344623;VariantGroup:4;CorrespondingGene:6833;RS#:151344623 | 11 |
We identified a novel compound heterozygous variant in @GENE$ @VARIANT$ (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 stop codon in position... | 6,567,512 | BBS1;11641 | BBS2;12122 | c.1285dup;tmVar:c|DUP|1285||;HGVS:c.1285dup;VariantGroup:20;CorrespondingGene:582 | c.763A > T;tmVar:c|SUB|A|763|T;HGVS:c.763A>T;VariantGroup:29;CorrespondingGene:55212 | 0no label |
Interestingly, one FALS proband carried 3 variants, each of which has previously been reported as pathogenic: SOD1 p.G38R, ANG p.P136L, and @GENE$ p.T1249I. Nine apparently sporadic subjects had variants in multiple genes (Table 4), but only two were well-established ALS mutations: TARDBP @VARIANT$ was found in combina... | 4,293,318 | DCTN1;3011 | VAPB;36163 | p.G287S;tmVar:p|SUB|G|287|S;HGVS:p.G287S;VariantGroup:0;CorrespondingGene:23435;RS#:80356719;CA#:586459 | p.M170I;tmVar:p|SUB|M|170|I;HGVS:p.M170I;VariantGroup:45;CorrespondingGene:9217;RS#:143144050;CA#:9924276 | 0no label |
Two SALS patients carried multiple ALS-associated variants that are rare in population databases (ANG @VARIANT$ with VAPB p.M170I and @GENE$ p.R408C with SETX @VARIANT$ and @GENE$ p.T14I). | 4,293,318 | TAF15;131088 | SETX;41003 | p.K41I;tmVar:p|SUB|K|41|I;HGVS:p.K41I;VariantGroup:28;CorrespondingGene:283;RS#:1219381953 | p.I2547T;tmVar:p|SUB|I|2547|T;HGVS:p.I2547T;VariantGroup:58;CorrespondingGene:23064;RS#:151117904;CA#:233108 | 0no label |
The ages of onset of the patients with the @GENE$ variants reported in this study were later than juvenile ALS onset, which generally manifests before 25 years of age. Previous studies suggested that heterozygous variants in the ALS2 may be causative for adult-onset sALS. @GENE$ encodes three protein isoforms that hav... | 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 |
Proband 17 inherited CHD7 @VARIANT$ and @GENE$ @VARIANT$ variants from his unaffected father and mother, respectively. Notably, proband P05 in family 05 harbored a de novo @GENE$ c.1664-2A>C variant. | 8,152,424 | CDON;22996 | FGFR1;69065 | p. Trp1994Gly;tmVar:p|SUB|W|1994|G;HGVS:p.W1994G;VariantGroup:14;CorrespondingGene:55636 | p. Val969Ile;tmVar:p|SUB|V|969|I;HGVS:p.V969I;VariantGroup:13;CorrespondingGene:50937;RS#:201012847;CA#:3044125 | 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 | G672E;tmVar:p|SUB|G|672|E;HGVS:p.G672E;VariantGroup:2;CorrespondingGene:5172;RS#:111033309;CA#:261423 | S166N;tmVar:p|SUB|S|166|N;HGVS:p.S166N;VariantGroup:22;CorrespondingGene:23985 | 0no label |
The most common mutation was p.R1110Q (@GENE$: c.3329G>A), which was found in 5 patients, accounting for 11% of all the cases. Of the 3 novel variants in DUOX2, @VARIANT$ was a frameshift mutation and had a potential deleterious effect on protein function and p.D137E and @VARIANT$ were missense mutations located in the... | 7,248,516 | DUOX2;9689 | TPO;461 | p.T803fs;tmVar:p|FS|T|803||;HGVS:p.T803fsX;VariantGroup:61;CorrespondingGene:50506 | p.E389K;tmVar:p|SUB|E|389|K;HGVS:p.E389K;VariantGroup:1;CorrespondingGene:7253;RS#:377424991 | 0no label |
Surprisingly, we identified two missense mutations in the proband: NM_001257180.2, exon10, c.1787A>G, @VARIANT$ in SLC20A2 (Figure 1c) and NM_002609.4, exon3, c.317G>C, @VARIANT$, rs544478083 in @GENE$ (Figure 1d). Subsequently, we further detected the distribution of the two variants in this family and found that the ... | 8,172,206 | PDGFRB;1960 | SLC20A2;68531 | p.His596Arg;tmVar:p|SUB|H|596|R;HGVS:p.H596R;VariantGroup:2;CorrespondingGene:6575 | p.Arg106Pro;tmVar:p|SUB|R|106|P;HGVS:p.R106P;VariantGroup:1;CorrespondingGene:5159;RS#:544478083 | 0no label |
These findings support the importance of @GENE$ as a structural and signalling molecule in cardiomyocytes, and may indicate the modifier role that missense variations in LAMA4 play in the disease. Digenic heterozygosity has been described in some DCM cases and is often associated with a severe presentation of DCM. Moll... | 6,359,299 | LAMA4;37604 | MYH7;68044 | L1038P;tmVar:p|SUB|L|1038|P;HGVS:p.L1038P;VariantGroup:8;CorrespondingGene:4625;RS#:551897533;CA#:257817954 | R326Q;tmVar:p|SUB|R|326|Q;HGVS:p.R326Q;VariantGroup:6;CorrespondingGene:4607;RS#:34580776;CA#:16212 | 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 @VARIANT$; @VARIANT$ of KAL1) and NELF/TACR3 (c. 1160-13C>T of @GENE$ and c.824G>A; p.Trp275X of @GENE$). | 3,888,818 | NELF;10648 | TACR3;824 | c.488_490delGTT;tmVar:p|DEL|488_490|V;HGVS:p.488_490delV;VariantGroup:8;CorrespondingGene:26012 | p.Cys163del;tmVar:p|DEL|163|C;HGVS:p.163delC;VariantGroup:10;CorrespondingGene:3730 | 0no label |
Two SALS patients carried multiple ALS-associated variants that are rare in population databases (ANG @VARIANT$ with @GENE$ @VARIANT$ and @GENE$ p.R408C with SETX p.I2547T and SETX p.T14I). | 4,293,318 | VAPB;36163 | TAF15;131088 | p.K41I;tmVar:p|SUB|K|41|I;HGVS:p.K41I;VariantGroup:28;CorrespondingGene:283;RS#:1219381953 | p.M170I;tmVar:p|SUB|M|170|I;HGVS:p.M170I;VariantGroup:45;CorrespondingGene:9217;RS#:143144050;CA#:9924276 | 0no label |
(E) The @GENE$ mutation @VARIANT$ and WNT10A mutation @VARIANT$ were found in patient S3, who inherited the mutant allele from his mother. (F) The mutations c.1045G>A in EDA and c.511C>T in @GENE$ were found in patient S4, but his mother's DNA sample could not be obtained. | 3,842,385 | EDA;1896 | WNT10A;22525 | c.466C>T;tmVar:c|SUB|C|466|T;HGVS:c.466C>T;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | c.637G>A;tmVar:c|SUB|G|637|A;HGVS:c.637G>A;VariantGroup:4;CorrespondingGene:80326;RS#:147680216;CA#:211313 | 0no label |
Subsequently, genetic testing for the LQT1, LQT2, LQT3, LQT5, and LQT6 genes identified a heterozygous c.3092_3096dup (@VARIANT$) mutation of the KCNH2 gene (@GENE$) and a heterozygous c.170T > C (@VARIANT$) unclassified variant (UV) of the KCNE2 gene (LQT6). The UV (missense mutation) of the KCNE2 gene is likely a pat... | 6,610,752 | LQT2;201 | LQT6;71688 | p.Arg1033ValfsX26;tmVar:p|FS|R|1033|V|26;HGVS:p.R1033VfsX26;VariantGroup:1;CorrespondingGene:3757 | p.Ile57Thr;tmVar:p|SUB|I|57|T;HGVS:p.I57T;VariantGroup:0;CorrespondingGene:9992;RS#:794728493 | 0no label |
The mutations of KCNH2 p.307_308del and @GENE$ @VARIANT$ were found in the proband by WES and validated as positive by Sanger sequencing. Additionally, the heterozygous SCN5A p.R1865H was carried by I: 1 and II: 2, but not carried by I: 2 (Figure 1a). Except II: 1, other family members without cardiac event or ca... | 8,739,608 | SCN5A;22738 | KCNH2;201 | 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 |
Additionally, the nucleotide sequence showed a monoallelic C to T transition at nucleotide 511 (c.511C>T) of the coding sequence in exon 3 of @GENE$, which results in the substitution of @VARIANT$. DNA sequencing of the parents' genome revealed that both mutant alleles were from their mother (Fig. 2A), who carried a he... | 3,842,385 | WNT10A;22525 | EDA;1896 | Arg at residue 171 to Cys;tmVar:p|SUB|R|171|C;HGVS:p.R171C;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | c.769G>C;tmVar:c|SUB|G|769|C;HGVS:c.769G>C;VariantGroup:0;CorrespondingGene:1896;RS#:1057517882;CA#:16043329 | 0no label |
In family 18287 we detected a possible bilineal inheritance, with variants in both @GENE$ and PKD2 (Figure 1). Two pregnancies were interrupted due to a prenatal finding of polycystic kidney disease at ultrasound examination at 20 and 13 gestational weeks, respectively. The mother was 33 year old; she had multicystic b... | 7,224,062 | PKD1;250 | PKD2;20104 | Cys331Thr;tmVar:p|SUB|C|331|T;HGVS:p.C331T;VariantGroup:1;CorrespondingGene:23193;RS#:144118755;CA#:6050907 | Arg872Gly;tmVar:p|SUB|R|872|G;HGVS:p.R872G;VariantGroup:9;CorrespondingGene:5311;RS#:755226061;CA#:3004303 | 0no label |
In Family A, there was digenic inheritance of two heterozygous variants: a novel variant in @GENE$ (c.3925G > A, @VARIANT$) and a known DCM mutation in @GENE$ (c.2770G > A; @VARIANT$). | 6,359,299 | LAMA4;37604 | MYH7;68044 | p.Asp1309Asn;tmVar:p|SUB|D|1309|N;HGVS:p.D1309N;VariantGroup:1;CorrespondingGene:3910;RS#:782046057 | p.Glu924Lys;tmVar:p|SUB|E|924|K;HGVS:p.E924K;VariantGroup:0;CorrespondingGene:4625;RS#:121913628;CA#:13034 | 11 |
In Gata4ki mice with @VARIANT$ mutation interaction of Gata4 with cofactor Fog is abrogated, and consequently animals display anomalies of testis development. Moreover, GATA4 functionally interacts with NR5A1 in Sertoli cell cultures to positively regulate the expression of AMH, and therefore, it has been reported that... | 5,893,726 | GATA;6699 | AMH;68060 | p.Val217Gly;tmVar:p|SUB|V|217|G;HGVS:p.V217G;VariantGroup:6;CorrespondingGene:14463 | p.Cys238Arg;tmVar:p|SUB|C|238|R;HGVS:p.C238R;VariantGroup:0;CorrespondingGene:2626 | 0no label |
A male (ID041), unrelated to ID104, carried heterozygous missense variants c.1513G > A (@VARIANT$) in @GENE$ and c.353A > G (@VARIANT$) in @GENE$. He was seen at 7 years and 10 months and, at that time, was severely developmentally delayed in multiple domains (motor, cognitive, and language). | 7,463,850 | EHMT1;11698 | MFSD8;115814 | p.Gly505Ser;tmVar:p|SUB|G|505|S;HGVS:p.G505S;VariantGroup:4;CorrespondingGene:79813;RS#:757679895;CA#:5374656 | p.Asn118Ser;tmVar:p|SUB|N|118|S;HGVS:p.N118S;VariantGroup:5;CorrespondingGene:256471;RS#:774112195;CA#:3077496 | 11 |
None of the variants in genes previously associated with HI segregated with the HI phenotype with the exception of the @GENE$ [GRCh37/hg19; chr10:@VARIANT$; NM_033056: c.3101G > A; @VARIANT$] and @GENE$ [GRCh37/hg19; chr17:72915838C > T; NM_173477:c.1093G > A; p.(Asp365Asn)] variants which displayed digenic inheritance... | 6,053,831 | PCDH15;23401 | USH1G;56113 | 55719513C > T;tmVar:g|SUB|C|55719513|T;HGVS:g.55719513C>T;VariantGroup:5;CorrespondingGene:65217 | p.(Arg1034His);tmVar:p|SUB|R|1034|H;HGVS:p.R1034H;VariantGroup:2;CorrespondingGene:124590 | 0no label |
Results Family with inherited neutropaenia, monocytosis and hearing impairment associated with mutations in @GENE$ and @GENE$. Pedigree, phenotypes and mutation status are indicated as per the key provided (a). Causative heterozygous mutations in GFI1 (@VARIANT$/c.1145A > G) and MYO6 (@VARIANT$/c.3526A > C) were identi... | 7,026,993 | GFI1;3854 | MYO6;56417 | p.N382S;tmVar:p|SUB|N|382|S;HGVS:p.N382S;VariantGroup:1;CorrespondingGene:2672;RS#:28936381;CA#:119872 | p.I1176L;tmVar:p|SUB|I|1176|L;HGVS:p.I1176L;VariantGroup:2;CorrespondingGene:4646;RS#:755922465;CA#:141060203 | 11 |
Three rare missense variants (R2034Q, @VARIANT$, 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 | L2118V;tmVar:p|SUB|L|2118|V;HGVS:p.L2118V;VariantGroup:13;CorrespondingGene:80208;RS#:766851227;CA#:7534152 | Q84H;tmVar:p|SUB|Q|84|H;HGVS:p.Q84H;VariantGroup:43;CorrespondingGene:29978 | 0no label |
Her mother with @VARIANT$ in COL4A5 and her father with a missense mutation @VARIANT$ in COL4A4 had intermittent hematuria and proteinuria. In proband of family 29, in addition to a glycine substitution (p. (Gly1119Ala)) in @GENE$ in the heterozygous state, there was another heterozygous nonsense mutation c.5026C > T i... | 6,565,573 | COL4A3;68033 | COL4A4;20071 | 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 |
We provide evidence that mutations in the @GENE$ and @GENE$ genes can interact to cause hearing loss in digenic heterozygotes. RESULTS Mutations at the gap junction proteins Cx26 and Cx31 can interact to cause non-syndromic deafness In total, 108 probands screened for mutations in the Cx26 gene were found to carry a si... | 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 |
Three rare missense variants (R2034Q, @VARIANT$, and E2003D) of the SPG11 gene were found. The high detection rate of missense variants of this gene is probably due to the large size of the coding region; therefore, we suggest that these SPG11 variants are unlikely to be deleterious. Variants in the @GENE$ ... | 6,707,335 | SPG11;41614 | ubiquilin-2;81830 | L2118V;tmVar:p|SUB|L|2118|V;HGVS:p.L2118V;VariantGroup:13;CorrespondingGene:80208;RS#:766851227;CA#:7534152 | Q84H;tmVar:p|SUB|Q|84|H;HGVS:p.Q84H;VariantGroup:43;CorrespondingGene:29978 | 0no label |
Molecular genetic studies A previously described homozygous @GENE$ nonsense mutation (@VARIANT$, p. R434*) had initially been identified in P1 and P2, for which their parents and unaffected sibling were heterozygous (Fig. 1). DNA was not available from the deceased sibling. The severity of the CH prompted investigation... | 5,587,079 | DUOX2;9689 | DUOX1;68136 | c.1300C>T;tmVar:c|SUB|C|1300|T;HGVS:c.1300C>T;VariantGroup:0;CorrespondingGene:50506;RS#:119472026;CA#:116636 | c.1823-1G>C;tmVar:c|SUB|G|1823-1|C;HGVS:c.1823-1G>C;VariantGroup:17;CorrespondingGene:53905 | 11 |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the @GENE$ gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and @GENE$ (c.1037... | 7,877,624 | MITF;4892 | 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 |
Results Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, @VARIANT$), TOR2A (NM_130459.3: @VARIANT$, p.Arg190Cys), and ATP2A3 (NM_005173.3: c.1966C>T, p.Arg656Cys) were identified in four independent multigenerational pedigrees... | 6,081,235 | DNAH17;72102 | UNC13B;31376 | p.Arg37Trp;tmVar:p|SUB|R|37|W;HGVS:p.R37W;VariantGroup:10;CorrespondingGene:80346;RS#:780399718;CA#:4663211 | c.568C>T;tmVar:c|SUB|C|568|T;HGVS:c.568C>T;VariantGroup:12;CorrespondingGene:27433;RS#:376074923;CA#:5250615 | 0no label |
Two SALS patients carried multiple ALS-associated variants that are rare in population databases (@GENE$ p.K41I with @GENE$ p.M170I and TAF15 @VARIANT$ with SETX @VARIANT$ and SETX p.T14I). | 4,293,318 | ANG;74385 | VAPB;36163 | p.R408C;tmVar:p|SUB|R|408|C;HGVS:p.R408C;VariantGroup:9;CorrespondingGene:8148;RS#:200175347;CA#:290041127 | p.I2547T;tmVar:p|SUB|I|2547|T;HGVS:p.I2547T;VariantGroup:58;CorrespondingGene:23064;RS#:151117904;CA#:233108 | 0no label |
Whole-exome sequencing testing more than 50 genes known to cause myopathy revealed variants in the COL6A3 (@VARIANT$), @GENE$ (rs143445685), @GENE$ (@VARIANT$), and DES (rs144901249) genes. | 6,180,278 | RYR1;68069 | CAPN3;52 | rs144651558;tmVar:rs144651558;VariantGroup:6;CorrespondingGene:1293;RS#:144651558 | rs138172448;tmVar:rs138172448;VariantGroup:2;CorrespondingGene:825;RS#:138172448 | 0no label |
In patient AVM226, we identified the compound heterozygous variants c.3775G>A (@VARIANT$) 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 | p.Val1259Ile;tmVar:p|SUB|V|1259|I;HGVS:p.V1259I;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 |
Two different GJB3 mutations (N166S and A194T) occurring in compound heterozygosity with the 235delC and 299delAT of @GENE$ were identified in three unrelated families (235delC/N166S, 235delC/@VARIANT$ and @VARIANT$/A194T). Neither of these mutations in @GENE$ was detected in DNA from 200 unrelated Chinese controls. | 2,737,700 | GJB2;2975 | Cx31;7338 | 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 |
To investigate the role of GJB3 variations along with GJB2 mutations for a possible combinatory allelic disease inheritance, we have screened patients with heterozygous @GENE$ mutations for variants in Cx31 by sequencing. Analysis of the entire coding region of the @GENE$ gene revealed the presence of two different mis... | 2,737,700 | GJB2;2975 | Cx31;7338 | 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 | 235delC;tmVar:c|DEL|235|C;HGVS:c.235delC;VariantGroup:1;CorrespondingGene:2706;RS#:80338943 | 0no label |
SCN5A p.R1865 and KCNH2 p.307_308 of amino acid sequences were highly conserved across the common species Sanger sequencing for SCN5A and @GENE$ mutations. KCNH2 p.307_308del and SCN5A p.R1865H of the proband were validated as positive by Sanger sequencing. Additionally, I: 1 and II: 2 carried with the heterozygous for... | 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 |
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$, c.238_239dupC in USH1C, and c.2299delG and @VARIANT$ in @GENE$. Therefore, in the process of designing any st... | 3,125,325 | MYO7A;219 | USH2A;66151 | c.3719G>A;tmVar:c|SUB|G|3719|A;HGVS:c.3719G>A;VariantGroup:87;CorrespondingGene:4647;RS#:542400234;CA#:5545997 | c.10712C>T;tmVar:c|SUB|C|10712|T;HGVS:c.10712C>T;VariantGroup:83;CorrespondingGene:7399;RS#:202175091;CA#:262060 | 0no label |
The detected R572W variant affects the nuclear localization signal 2 (amino acids 568-574) of the @GENE$ protein. A previously characterized pathogenic nonsense variant (G1177X) and a rare missense alteration (R1499H) were detected in the ALS2 gene, both in heterozygous form. The alsin protein encoded by the ALS2 g... | 6,707,335 | CCNF;1335 | ALS2;23264 | 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 |
Interestingly, one FALS proband carried 3 variants, each of which has previously been reported as pathogenic: SOD1 p.G38R, ANG @VARIANT$, and @GENE$ p.T1249I. 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 combina... | 4,293,318 | DCTN1;3011 | VAPB;36163 | p.P136L;tmVar:p|SUB|P|136|L;HGVS:p.P136L;VariantGroup:7;CorrespondingGene:283;RS#:121909543;CA#:258112 | p.M170I;tmVar:p|SUB|M|170|I;HGVS:p.M170I;VariantGroup:45;CorrespondingGene:9217;RS#:143144050;CA#:9924276 | 0no label |
Results Cosegregating deleterious variants (GRCH37/hg19) in CACNA1A (NM_001127222.1: c.7261_7262delinsGT, p.Pro2421Val), REEP4 (NM_025232.3: c.109C>T, p.Arg37Trp), TOR2A (NM_130459.3: c.568C>T, p.Arg190Cys), and @GENE$ (NM_005173.3: c.1966C>T, @VARIANT$) were identified in four independent multigenerational pedigrees. ... | 6,081,235 | ATP2A3;69131 | VPS13C;41188 | p.Arg656Cys;tmVar:p|SUB|R|656|C;HGVS:p.R656C;VariantGroup:21;CorrespondingGene:489;RS#:140404080;CA#:8297011 | c.989_990del;tmVar:c|DEL|989_990|;HGVS:c.989_990del;VariantGroup:16;CorrespondingGene:9630;RS#:750424668;CA#:5094137 | 0no label |
Two unrelated KS patients had heterozygous NELF mutations and mutation in a second gene: NELF/@GENE$ (c.757G>A; @VARIANT$ of NELF and c.488_490delGTT; p.Cys163del of KAL1) and NELF/@GENE$ (c. 1160-13C>T of NELF and c.824G>A; @VARIANT$ of TACR3). | 3,888,818 | KAL1;55445 | TACR3;824 | p.Ala253Thr;tmVar:p|SUB|A|253|T;HGVS:p.A253T;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 |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, SOX10, SNAI2, and @GENE$) were searched and a novel rare heterozygous deletion mutation (c.965delA; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in @GENE$ (c.607C>T; @VARIANT$) and TYRO3 (c.1037T... | 7,877,624 | TYRO3;4585 | SNAI3;8500 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, @GENE$, @GENE$, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; p.Arg203Cys) and TYRO3 (c.1037... | 7,877,624 | SOX10;5055 | SNAI2;31127 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;CorrespondingGene:4286 | p.Ile346Asn;tmVar:p|SUB|I|346|N;HGVS:p.I346N;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
II: 1 carried the digenic heterozygous mutations of @GENE$ @VARIANT$ and @GENE$ p.R1865H. I: 1 and II: 2 were heterozygous for SCN5A @VARIANT$. Except II: 1, other family members did not carry KCNH2 mutation. | 8,739,608 | KCNH2;201 | SCN5A;22738 | p.307_308del;tmVar:p|DEL|307_308|;HGVS:p.307_308del;VariantGroup:16;CorrespondingGene:3757 | p.R1865H;tmVar:p|SUB|R|1865|H;HGVS:p.R1865H;VariantGroup:1;CorrespondingGene:6331;RS#:370694515;CA#:64651 | 0no label |
Variants in all known WS candidate genes (EDN3, EDNRB, @GENE$, @GENE$, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; @VARIANT$) and TYRO3 (c.103... | 7,877,624 | MITF;4892 | PAX3;22494 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | p.Arg203Cys;tmVar:p|SUB|R|203|C;HGVS:p.R203C;VariantGroup:1;CorrespondingGene:333929;RS#:149676512;CA#:8229366 | 0no label |
Compared to WT (wild-type) proteins, we found that the ability of GFP-CYP1B1 @VARIANT$ and GFP-@GENE$ E229K to immunoprecipitate HA-TEK E103D and HA-@GENE$ @VARIANT$, respectively, was significantly diminished. | 5,953,556 | CYP1B1;68035 | TEK;397 | A115P;tmVar:p|SUB|A|115|P;HGVS:p.A115P;VariantGroup:0;CorrespondingGene:1545;RS#:764338357;CA#:1620052 | Q214P;tmVar:p|SUB|Q|214|P;HGVS:p.Q214P;VariantGroup:10;CorrespondingGene:7010 | 0no label |
CSS161458 had a heterozygous splicing variant @VARIANT$ in RIPPLY1, as described above, and a heterozygous missense variant c.464G>T(@VARIANT$) in MYOD1 was also identified. Although no direct interaction between @GENE$ and @GENE$ has been reported, they may together dysregulate the TBX6 pathway given the deleterious... | 7,549,550 | RIPPLY1;138181 | MYOD1;7857 | c.156-1G>C;tmVar:c|SUB|G|156-1|C;HGVS:c.156-1G>C;VariantGroup:12;CorrespondingGene:92129 | p.Arg155Leu;tmVar:p|SUB|R|155|L;HGVS:p.R155L;VariantGroup:2;CorrespondingGene:4654;RS#:757176822;CA#:5906444 | 0no label |
These two individuals were heterozygous carriers of @VARIANT$ mutation in @GENE$ and p.V255M in GGCX. Since heterozygous carriers of p.R1141X in ABCC6 alone do not manifest PXE and GGCX mutations with respect to coagulation disorder are recessive, these findings suggest that the skin phenotype in these two individuals ... | 2,900,916 | ABCC6;55559 | MGP;693 | p.R1141X;tmVar:p|SUB|R|1141|X;HGVS:p.R1141X;VariantGroup:6;CorrespondingGene:368;RS#:72653706;CA#:129115 | p.S300F;tmVar:p|SUB|S|300|F;HGVS:p.S300F;VariantGroup:16;CorrespondingGene:2677;RS#:121909684;CA#:214948 | 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 |
We identified a novel compound heterozygous variant in @GENE$ @VARIANT$ (p.(Arg429Profs*72); a likely pathogenic novel variant affecting the conserved residue 354 in the functional domain of BBS2 (@VARIANT$; p.(Asn354Lys)); a pathogenic new homozygous nucleotide change in BBS7 that leads to a stop codon in position 255... | 6,567,512 | BBS1;11641 | BBS6;10318 | c.1285dup;tmVar:c|DUP|1285||;HGVS:c.1285dup;VariantGroup:20;CorrespondingGene:582 | c.1062C > G;tmVar:c|SUB|C|1062|G;HGVS:c.1062C>G;VariantGroup:22;CorrespondingGene:583 | 0no label |
Compared to WT (wild-type) proteins, we found that the ability of GFP-CYP1B1 A115P and GFP-CYP1B1 E229K to immunoprecipitate HA-TEK E103D and HA-TEK @VARIANT$, respectively, was significantly diminished. GFP-CYP1B1 R368H also exhibited relatively reduced ability to immunoprecipitate HA-TEK I148T (~70%). No significant ... | 5,953,556 | TEK;397 | CYP1B1;68035 | Q214P;tmVar:p|SUB|Q|214|P;HGVS:p.Q214P;VariantGroup:10;CorrespondingGene:7010 | A115P;tmVar:p|SUB|A|115|P;HGVS:p.A115P;VariantGroup:0;CorrespondingGene:1545;RS#:764338357;CA#:1620052 | 0no label |
Based on these findings, we conclude that, unlike LQTS-associated mutations, the @GENE$-@VARIANT$ variant does not severely affect the function of the channel. 2.3.2. @GENE$-p.C108Y Exhibits a Dominant-Negative Loss-of-Function Heterologous expression studies demonstrated that KCNH2-@VARIANT$ is a non-functional channe... | 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.C108Y;tmVar:p|SUB|C|108|Y;HGVS:p.C108Y;VariantGroup:3;CorrespondingGene:3757 | 0no label |
This patient with the @VARIANT$ NELF missense mutation also had a hemizygous KAL1 deletion of the completely conserved @VARIANT$ within the whey-acidic-protein (WAP) domain that forms a disulphide bridge with Cys134 of anosmin-1 (Figure S1C,D). Unilateral renal agenesis in this patient is likely related to this deleter... | 3,888,818 | NELF;10648 | TACR3;824 | p.Ala253Thr;tmVar:p|SUB|A|253|T;HGVS:p.A253T;VariantGroup:3;CorrespondingGene:26012;RS#:142726563;CA#:5370407 | Cys163;tmVar:p|Allele|C|163;VariantGroup:9;CorrespondingGene:3730 | 0no label |
Variants in all known WS candidate genes (EDN3, @GENE$, @GENE$, PAX3, SOX10, SNAI2, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (@VARIANT$; p.Arg203Cys) and TYRO3 (c.10... | 7,877,624 | EDNRB;89 | MITF;4892 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;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 |
Functional characterisation of AIS-associated FLNB variants According to alignment to the @GENE$ protein domain, most of the AIS-associated FLNB variants are located within immunoglobulin-like filamin repeat regions, some of which belong to the domain of interaction with @GENE$ (figure 2A). Of note, @VARIANT$ is loca... | 7,279,190 | FLNB;37480 | FLNA;1119 | p.R199Q;tmVar:p|SUB|R|199|Q;HGVS:p.R199Q;VariantGroup:0;CorrespondingGene:79989;RS#:1175244100 | p.A2282T;tmVar:p|SUB|A|2282|T;HGVS:p.A2282T;VariantGroup:6;CorrespondingGene:2317;RS#:1339176246 | 0no label |
Results Family with inherited neutropaenia, monocytosis and hearing impairment associated with mutations in @GENE$ and MYO6. Pedigree, phenotypes and mutation status are indicated as per the key provided (a). Causative heterozygous mutations in GFI1 (@VARIANT$/c.1145A > G) and @GENE$ (@VARIANT$/c.3526A > C) were identi... | 7,026,993 | GFI1;3854 | MYO6;56417 | p.N382S;tmVar:p|SUB|N|382|S;HGVS:p.N382S;VariantGroup:1;CorrespondingGene:2672;RS#:28936381;CA#:119872 | p.I1176L;tmVar:p|SUB|I|1176|L;HGVS:p.I1176L;VariantGroup:2;CorrespondingGene:4646;RS#:755922465;CA#:141060203 | 0no label |
Other family members who have inherited @GENE$ @VARIANT$ and TNFRSF13B/TACI C104R mutations are shown. 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-t... | 5,671,988 | TCF3;2408 | TACI;49320 | 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 |
Only 9 mutations previously reported as recurrent were detected in our series of patients (i.e. 11% of the mutations), specifically, c.1996C>T, @VARIANT$, c.1556G>A, c.494C>T, c.3719G>A and c.5749G>T in @GENE$, c.238_239dupC in USH1C, and c.2299delG and @VARIANT$ in @GENE$. Therefore, in the process of designing any st... | 3,125,325 | MYO7A;219 | USH2A;66151 | c.223delG;tmVar:c|DEL|223|G;HGVS:c.223delG;VariantGroup:77;CorrespondingGene:4647;RS#:876657415 | c.10712C>T;tmVar:c|SUB|C|10712|T;HGVS:c.10712C>T;VariantGroup:83;CorrespondingGene:7399;RS#:202175091;CA#:262060 | 0no label |
Analysis of the entire coding region of the @GENE$ gene revealed the presence of two different missense mutations (N166S and A194T) occurring in compound heterozygosity along with the 235delC and @VARIANT$ of @GENE$ in 3 simplex families (235delC/N166S, 235delC/A194T and 299delAT/A194T). In family A, a profoundly heari... | 2,737,700 | Cx31;7338 | GJB2;2975 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | 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 |
Variants in all known WS candidate genes (EDN3, EDNRB, MITF, PAX3, SOX10, @GENE$, and TYRO3) were searched and a novel rare heterozygous deletion mutation (c.965delA; @VARIANT$) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; p.Arg203Cys) and @GENE$ (@VARIA... | 7,877,624 | SNAI2;31127 | TYRO3;4585 | p.Asn322fs;tmVar:p|FS|N|322||;HGVS:p.N322fsX;VariantGroup:3;CorrespondingGene:4286 | c.1037T>A;tmVar:c|SUB|T|1037|A;HGVS:c.1037T>A;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
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 @GENE$ mutations (N166S and A194T) occurring in compound heterozygosity with the 235delC and @VARIANT$ of GJB2 were identified in three unrelate... | 2,737,700 | GJB2;2975 | GJB3;7338 | 299delAT;tmVar:c|DEL|299|AT;HGVS:c.299delAT;VariantGroup:12;CorrespondingGene:2706 | A194T;tmVar:c|SUB|A|194|T;HGVS:c.194A>T;VariantGroup:4;CorrespondingGene:2707;RS#:117385606;CA#:118313 | 0no label |
Interestingly, one FALS proband carried 3 variants, each of which has previously been reported as pathogenic: SOD1 @VARIANT$, @GENE$ p.P136L, and DCTN1 p.T1249I. 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 comb... | 4,293,318 | ANG;74385 | SETX;41003 | p.G38R;tmVar:p|SUB|G|38|R;HGVS:p.G38R;VariantGroup:50;CorrespondingGene:6647;RS#:121912431;CA#:257311 | p.P525L;tmVar:p|SUB|P|525|L;HGVS:p.P525L;VariantGroup:62;CorrespondingGene:2521;RS#:886041390;CA#:10603390 | 0no label |
The @VARIANT$ (c.1045G>A) mutation in exon 9 of @GENE$ and heterozygous @VARIANT$ (c.511C>T) mutation in exon 3 of WNT10A were detected. These mutations were not found in his father's genome, but because his mother's DNA sample was unavailable, the origin of the mutant alleles was not clear (Fig. 2F). All novel mut... | 3,842,385 | EDA;1896 | WNT10A;22525 | 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 |
Moreover, the presence of other variants (@GENE$-p.R583H, KCNH2-@VARIANT$, and @GENE$-@VARIANT$) could further enhance the effects of the mutant channels, thus resulting in incomplete penetrance and variable expressivity of the phenotype. | 5,578,023 | KCNQ1;85014 | KCNE1;3753 | p.K897T;tmVar:p|SUB|K|897|T;HGVS:p.K897T;VariantGroup:0;CorrespondingGene:3757;RS#:1805123;CA#:7162 | p.G38S;tmVar:p|SUB|G|38|S;HGVS:p.G38S;VariantGroup:1;CorrespondingGene:3753;RS#:1805127;CA#:131330 | 0no label |
Future studies will focus on determining how double homozygous mutations in @GENE$ (@VARIANT$) and @GENE$ (@VARIANT$) result in increased intracellular pro-COL1A1 levels and increased pro-COLA1 secretion. | 4,853,519 | SEC23A;4642 | MAN1B1;5230 | 1200G>C;tmVar:c|SUB|G|1200|C;HGVS:c.1200G>C;VariantGroup:0;CorrespondingGene:10484;RS#:866845715;CA#:259543384 | 1000C>T;tmVar:c|SUB|C|1000|T;HGVS:c.1000C>T;VariantGroup:4;CorrespondingGene:11253;RS#:387906886;CA#:129197 | 11 |
(E) The EDA mutation @VARIANT$ and @GENE$ mutation c.637G>A were found in patient S3, who inherited the mutant allele from his mother. (F) The mutations c.1045G>A in @GENE$ and @VARIANT$ in WNT10A were found in patient S4, but his mother's DNA sample could not be obtained. | 3,842,385 | WNT10A;22525 | EDA;1896 | c.466C>T;tmVar:c|SUB|C|466|T;HGVS:c.466C>T;VariantGroup:5;CorrespondingGene:1896;RS#:132630313;CA#:255655 | c.511C>T;tmVar:c|SUB|C|511|T;HGVS:c.511C>T;VariantGroup:3;CorrespondingGene:80326;RS#:116998555;CA#:2113955 | 0no label |
We observed that in 5 PCG cases heterozygous CYP1B1 mutations (@VARIANT$, p.E229 K, and p.R368H) co-occurred with heterozygous @GENE$ mutations (@VARIANT$, p.I148T, p.Q214P, and p.G743A) indicating a potential digenic inheritance (Fig. 1a). None of the normal controls carried both the heterozygous combinations of @GENE... | 5,953,556 | TEK;397 | CYP1B1;68035 | p.A115P;tmVar:p|SUB|A|115|P;HGVS:p.A115P;VariantGroup:0;CorrespondingGene:1545;RS#:764338357;CA#:1620052 | p.E103D;tmVar:p|SUB|E|103|D;HGVS:p.E103D;VariantGroup:2;CorrespondingGene:7010;RS#:572527340;CA#:5015873 | 0no label |
Variants in all known WS candidate genes (@GENE$, EDNRB, MITF, PAX3, SOX10, @GENE$, and TYRO3) were searched and a novel rare heterozygous deletion mutation (@VARIANT$; p.Asn322fs) was identified in the MITF gene in both patients. Moreover, heterozygous missense variants in SNAI3 (c.607C>T; p.Arg203Cys) and TYRO3 (@VAR... | 7,877,624 | EDN3;88 | SNAI2;31127 | c.965delA;tmVar:c|DEL|965|A;HGVS:c.965delA;VariantGroup:4;CorrespondingGene:4286 | c.1037T>A;tmVar:c|SUB|T|1037|A;HGVS:c.1037T>A;VariantGroup:2;CorrespondingGene:7301;RS#:12148316;CA#:7494886 | 0no label |
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