ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4547C>T (p.Ser1516Leu)

gnomAD frequency: 0.00003  dbSNP: rs139300715
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000209885 SCV000265507 uncertain significance Severe myoclonic epilepsy in infancy 2021-09-01 criteria provided, single submitter research
GeneDx RCV000494091 SCV000582178 likely pathogenic not provided 2015-09-25 criteria provided, single submitter clinical testing The S1516L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The S1516L 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 alters a highly conserved position predicted to be in the cytoplasmic loop between the third and fourth homologous domains. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, variants in nearby residues (A1510G, M1511R, L1514S, P1519T) have been reported in the Human Gene Mutation Database in association with SCN1A-related disorders (Stenson et al., 2014), supporting the functional importance of this region of the protein. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Invitae RCV000702992 SCV000831870 likely benign Early infantile epileptic encephalopathy with suppression bursts 2021-10-13 criteria provided, single submitter clinical testing

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