ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.1261C>T (p.Arg421Trp)

gnomAD frequency: 0.00001  dbSNP: rs1208991974
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000800471 SCV000940189 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2024-01-13 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 422 of the CACNA1A protein (p.Arg422Trp). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with clinical features of CACNA1A-related conditions (PMID: 34806130). ClinVar contains an entry for this variant (Variation ID: 646230). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CACNA1A protein function. 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.
Revvity Omics, Revvity RCV003489885 SCV004234899 uncertain significance not provided 2023-11-07 criteria provided, single submitter clinical testing

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