ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.3765G>A (p.Met1255Ile)

dbSNP: rs2144871559
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002003141 SCV002275877 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2021-09-04 criteria provided, single submitter clinical testing This sequence change replaces methionine with isoleucine at codon 1256 of the CACNA1A protein (p.Met1256Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. 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"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV003985537 SCV004113692 uncertain significance CACNA1A-related disorder 2023-03-29 criteria provided, single submitter clinical testing The CACNA1A c.3765G>A variant is predicted to result in the amino acid substitution p.Met1255Ile. To our knowledge, this variant has not been reported in the literature or in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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