ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.985G>T (p.Gly329Cys) (rs781746113)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189077 SCV000242708 likely pathogenic not provided 2015-01-14 criteria provided, single submitter clinical testing p.Gly329Cys (GGT>TGT): c.985 G>T in exon 7 of the SCN1A gene (NM_001165963.1) A G329C variant that is likely pathogenic has been identified in the SCN1A gene. The G329C 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 G329C 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 within the extracellular loop between the S5 and S6 transmembrane segments of the first homologous domain of the SCN1A protein (Escayg et al., 2010), and multiple missense mutations in this region of the protein have been reported in association with SCN1A-related disorders in an external mutation database, supporting the functional importance of this region of the protein. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. 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 INFANTV2-EPIV2-1 panel(s).
Institute of Human Genetics, University of Leipzig Medical Center RCV001253376 SCV001429055 pathogenic Severe myoclonic epilepsy in infancy 2018-09-10 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Leipzig Medical Center RCV001255357 SCV001431687 pathogenic Intellectual disability 2020-08-03 criteria provided, single submitter clinical testing The variant c.985G>T, p.(Gly329Cys) was identified in an individual with neurodevelopmental disorder (NDD) and classified as Pathogenic according to ACMG guidelines. Inheritance for this variant was DNV .The variant likely explains the NDD in this individual.

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