ClinVar Miner

Submissions for variant NM_001165963.4(SCN1A):c.2985T>G (p.Phe995Leu) (rs794726746)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Bioinformatics, Peking University RCV000180857 SCV000221822 pathogenic Severe myoclonic epilepsy in infancy 2014-12-20 criteria provided, single submitter research
GeneDx RCV000188906 SCV000242536 uncertain significance not provided 2014-06-05 criteria provided, single submitter clinical testing p.Phe995Leu (TTT>TTG): c.2985 T>G in exon 16 of the SCN1A gene (NM_001165963.1) The F995L missense variant has been reported in association with Dravet syndrome in an external mutation database; however no information about the variant was available in the publication. 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. This substitution occurs at a conserved position in the cytoplasmic loop between the second and third homologous domains, and several other missense mutations (L990F, S993R, D998G) have been reported in this region of the protein in association with epilepsy. Additionally, in silico analysis predicts this variant is probably damaging to the protein structure/function. However, it is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.The variant is found in EPILEPSY panel(s).

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