ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.3355G>C (p.Ala1119Pro)

dbSNP: rs199745070
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489868 SCV000577482 uncertain significance not provided 2017-03-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1A gene. The A1120P variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A1120P variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A1120P variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved, and in silico analysis predicts this variant likely does not alter the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001046221 SCV001210115 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2019-03-05 criteria provided, single submitter clinical testing 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. 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: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with CACNA1A-related conditions. ClinVar contains an entry for this variant (Variation ID: 426909). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with proline at codon 1120 of the CACNA1A protein (p.Ala1120Pro). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and proline.

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