ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.2236T>G (p.Leu746Val) (rs772195737)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523681 SCV000621783 uncertain significance not provided 2017-10-18 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SCN2A gene. The L746V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The L746V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The L746V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Leucine are tolerated across species. It is predicted to be within the intracellular loop between the S6 transmembrane segment of the first homologous domain and the S1 transmembrane segment of the second homologous domain. However, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.

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