ClinVar Miner

Submissions for variant NM_001128840.3(CACNA1D):c.1372G>C (p.Glu458Gln)

dbSNP: rs1193226150
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
New York Genome Center RCV002227709 SCV002506792 uncertain significance Aldosterone-producing adenoma with seizures and neurological abnormalities 2021-06-27 criteria provided, single submitter clinical testing The c.1372G>C (p.Glu458Gln) variant in exon 9 of 48 of CACNA1D has not been reported in affected individuals in the available literature. This variant is absent in gnomAD v3 indicating it is not a common benign variant in the populations represented in this database. In silico predictors suggest this variant is Benign (REVEL score: 0.416) and tolerated (SIFT score: 0.2). Given the current evidence regarding its pathogenicity, the c.1372G>C (p.Glu458Gln) variant identified in the CACNA1D gene is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV003774682 SCV004654275 uncertain significance not provided 2024-05-26 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 458 of the CACNA1D protein (p.Glu458Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CACNA1D-related conditions. ClinVar contains an entry for this variant (Variation ID: 1679685). 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 not expected to disrupt CACNA1D protein function with a negative predictive value of 80%. 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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