ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2201G>A (p.Cys734Tyr) (rs1247949520)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001333847 SCV001526540 uncertain significance Generalized epilepsy with febrile seizures plus, type 2 2018-07-19 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
New York Genome Center RCV001542305 SCV001760990 uncertain significance Severe myoclonic epilepsy in infancy 2020-07-10 criteria provided, single submitter clinical testing The inherited c.2168G>A (p.Cys723Tyr) variant identified in the SCN1A gene substitutes a very well conserved Cystine for Tyrosine at amino acid 723/1999 (exon 16/29). This variant is found with low frequency in gnomAD(v3.0) (4 heterozygotes, 0 homozygotes; allele frequency: 2.90e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms predict this variant to be Deleterious (Provean; score:-10.59) and Damaging (SIFT; score:0.00) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Cys723 residue is not within a mapped domain of SCN1A (UniProtKB:P35498). Given the lack of compelling evidence for its pathogenicity, the inherited c.2168G>A (p.Cys723Tyr) variant identified in the SCN1A gene is reported as a Variant of Uncertain Significance.
GeneDx RCV001773669 SCV002003527 uncertain significance not provided 2020-10-16 criteria provided, single submitter clinical testing This substitution is predicted to be located in the cytoplasmic loop between the first and second homologous domains; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); Has not been previously published as pathogenic or benign to our knowledge

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