ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5122A>C (p.Ile1708Leu)

dbSNP: rs2144647855
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001964248 SCV002250885 likely pathogenic Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2022-06-27 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.Ile1709 amino acid residue in CACNA1A. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15240985, 15452324). 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. 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 isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1709 of the CACNA1A protein (p.Ile1709Leu).

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