ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.4094G>A (p.Gly1365Asp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services,Murdoch Childrens Research Institute RCV001089990 SCV001244982 pathogenic Severe myoclonic epilepsy in infancy 2018-06-21 criteria provided, single submitter clinical testing A heterozygous missense variant, NM_001165963.1(SCN1A):c.4094G>A, has been identified in exon 21 of 26 of the SCN1A gene. The variant is predicted to result in a moderate amino acid change from glycine to aspartic acid at position 1365 of the protein (NP_001159435.1(SCN1A):p.(Gly1365Asp)). The glycine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the ion transport domain. In silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G), and has previously been reported as a de novo mutation in association with severe myoclonic epilepsy in infancy (SMEI), however, no additional information was provided (SCN1A variant database). A different variant in the same codon resulting in a change to serine has also been reported to cause SMEI (SCN1A variant database). Analysis of parental samples indicated this variant is de novo. Based on the information available at the time of curation, this variant has been classified as PATHOGENIC.

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