ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.5851G>T (p.Ala1951Ser) (rs376656165)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479848 SCV000573585 uncertain significance not provided 2017-02-28 criteria provided, single submitter clinical testing The A1951S variant in the SCN1A gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The A1951S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1951S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret A1951S as a variant of uncertain significance
Invitae RCV001224688 SCV001396903 uncertain significance Early infantile epileptic encephalopathy 2019-07-12 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 1951 of the SCN1A protein (p.Ala1951Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with epilepsy (PMID: 28202706). ClinVar contains an entry for this variant (Variation ID: 423837). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). 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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