ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.505T>C (p.Ser169Pro) (rs796052957)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000188835 SCV000242465 likely pathogenic not provided 2014-04-10 criteria provided, single submitter clinical testing p.Ser169Pro (TCA>CCA): c.505 T>C in exon 4 of the SCN1A gene (NM_001165963.1) A S169P variant that is likely pathogenic has been identified in the SCN1A gene. The S169P variant has not been published as a mutation, nor has it been reported as a benign polymorphism 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 S169P 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 conserved position in transmembrane segment S2 in the 1st homologous domain, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense mutations in nearby residues (G163E, I171K, I171R) have been reported in association with Dravet syndrome and myoclonic epilepsy of infancy, supporting the functional importance of this region of the protein. Therefore, this variant is a strong candidate for a pathogenic mutation; however the possibility that it is a benign variant cannot be excluded. The variant is found in CHILD-EPI panel(s).
Foundation for Research in Genetics and Endocrinology, FRIGE's Institute of Human Genetics RCV000500830 SCV000590941 likely pathogenic Severe myoclonic epilepsy in infancy 2017-08-17 no assertion criteria provided clinical testing The variant is predicted to be damaging by SIFT, LRT, MutationTaster, PolyPhen-2, Mutation Assessor and FATHMM. The identified variant g= has been reported in the dbSNP database with an identification number rs796052957. In the Clin Var database,the clinical significance of this variant has been reported as 'likely pathogenic' (RCV000188835); however, clinical condition for the same has not been provided.

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