ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.5521G>A (p.Ala1841Thr)

gnomAD frequency: 0.00002  dbSNP: rs753229469
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000419634 SCV000523751 uncertain significance not provided 2016-02-02 criteria provided, single submitter clinical testing The A1842T variant in the CACNA1A gene has not been reported previously as a pathogenic variant,nor as a benign variant, to our knowledge. The A1842T variant was not observed in approximately6300 individuals of European and African American ancestry in the NHLBI Exome SequencingProject, indicating it is not a common benign variant in these populations. The A1842T variant is anon-conservative amino acid substitution, which occurs within cytoplasmic domain at a position thatis conserved across species. In silico analysis predicts this variant is probably damaging to the proteinstructure/function. We interpret A1842T as a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001051286 SCV001215432 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1842 of the CACNA1A protein (p.Ala1842Thr). This variant is present in population databases (rs753229469, gnomAD 0.009%). This missense change has been observed in individual(s) with CACNA1A-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 383371). 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 with a positive predictive value of 95%. 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.

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