ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.905A>G (p.Asp302Gly)

dbSNP: rs2059067761
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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 RCV001318930 SCV001509652 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-03-10 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Asp302 amino acid residue in CACNA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24486772, 25326637, 27066515, 27871455). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 1019492). This missense change has been observed in individual(s) with clinical features of CACNA1A-related conditions (Invitae). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 302 of the CACNA1A protein (p.Asp302Gly).
GeneDx RCV003318680 SCV004023126 uncertain significance not provided 2023-01-30 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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