ClinVar Miner

Submissions for variant NM_001040142.2(SCN2A):c.722T>G (p.Leu241Arg)

dbSNP: rs2467890178
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002371010 SCV002671408 likely pathogenic Inborn genetic diseases 2018-06-06 criteria provided, single submitter clinical testing The p.L241R variant (also known as c.722T>G), located in coding exon 6 of the SCN2A gene, results from a T to G substitution at nucleotide position 722. The leucine at codon 241 is replaced by arginine, an amino acid with dissimilar properties. This variant has been determined to be the result of a de novo mutation or germline mosaicism in one family with an isolated case of SCN2A-related epileptic encephalopathy (Ambry internal data). This alteration is located in the S4-S5 cytoplasmic domain of repeat I and is indicated to be structurally deleterious (Ambry internal data; Yan Z et al. Cell, 2017 Jul;170:470-482.e11). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV003098511 SCV003316989 likely pathogenic Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 2022-04-26 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with clinical features of SCN2A-related conditions (Invitae). In at least one individual the variant was observed to be de novo. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 241 of the SCN2A protein (p.Leu241Arg).

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