ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1213G>A (p.Ala405Thr) (rs121908245)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000431929 SCV000512440 uncertain significance not provided 2017-10-06 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1A gene. The A405T variant has been reported previously in three affected females from a family with a spectrum of phenotypes including episodic ataxia, progressive spinocerebellar ataxia, and familial hemiplegic migraine (Romaniello et al., 2010). Two male carriers in this family were reported to be unaffected, suggesting additional genetic and environmental factors may affect the clinical presentation (Romaniello et al., 2010). The A405T variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts the A405T variant is probably damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
UniProtKB/Swiss-Prot RCV000059289 SCV000090838 not provided Episodic ataxia type 2 no assertion provided not provided

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