ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5033G>A (p.Arg1678His)

gnomAD frequency: 0.00001  dbSNP: rs2055849544
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001039877 SCV001203427 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2023-10-02 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1679 of the CACNA1A protein (p.Arg1679His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 838346). 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. This variant disrupts the p.Arg1679 amino acid residue in CACNA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20129625, 34085110; Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille RCV001251920 SCV001427666 likely benign Intellectual disability 2019-01-01 no assertion criteria provided clinical testing

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