ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.251A>G (p.Tyr84Cys) (rs121917964)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255485 SCV000321935 pathogenic not provided 2021-05-26 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (Lek et al., 2016); Missense variants in this gene are often considered pathogenic (Stenson et al., 2014); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This substitution is predicted to be within the N-terminal cytoplasmic domain; This variant is associated with the following publications: (PMID: 19589774, 21248271, 32090326, 17347258, 23195492, 29933521, 31031587)
Invitae RCV000695650 SCV000824162 pathogenic Early infantile epileptic encephalopathy with suppression bursts 2019-07-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 84 of the SCN1A protein (p.Tyr84Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with severe myoclonic epilepsy of infancy (SMEI) or Dravet syndrome (PMID: 17347258, 23195492, 22050978). In at least one of these individuals the variant was reported to be de novo. ClinVar contains an entry for this variant (Variation ID: 68520). 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. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics,Fulgent Genetics RCV000763463 SCV000894240 likely pathogenic Familial hemiplegic migraine type 3; Severe myoclonic epilepsy in infancy; Generalized epilepsy with febrile seizures plus, type 2 2018-10-31 criteria provided, single submitter clinical testing
UniProtKB/Swiss-Prot RCV000059392 SCV000090916 not provided Severe myoclonic epilepsy in infancy no assertion provided not provided

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