ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.830G>A (p.Cys277Tyr) (rs1574264920)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000986911 SCV001136065 likely pathogenic Severe myoclonic epilepsy in infancy 2019-05-28 criteria provided, single submitter clinical testing
Invitae RCV001338678 SCV001532364 uncertain significance Early infantile epileptic encephalopathy with suppression bursts 2020-01-20 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 277 of the SCN1A protein (p.Cys277Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with clinical features of early infantile epileptic encephalopathy (Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant disrupts the p.Cys277 amino acid residue in SCN1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 18930999). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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