ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.5645G>T (p.Arg1882Leu) (rs794727444)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189182 SCV000242814 pathogenic not provided 2016-06-07 criteria provided, single submitter clinical testing The R1882L variant in the SCN2A gene has been reported previously as a de novo variant in an individual with intractable epilepsy, intellectual disability, microcephaly, optic atrophy, and hypotonia (Baasch et al., 2014). Additionally different missense variants at the same position (R1882Q, R1882G) have been reported in association with SCN2A-related disorders (Carvill et al., 2013; Schwarz et al., 2016). The R1882L variant 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 R1882L 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 occurs at a conserved position predicted to be within the C-terminal cytoplasmic domain of the protein, and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, the presence of R1882L is consistent with a diagnosis of a SCN2A-related disorder

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