ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.1723A>T (p.Met575Leu)

gnomAD frequency: 0.00002  dbSNP: rs1157777158
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001366387 SCV001562688 uncertain significance Long QT syndrome 2023-10-06 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 575 of the CACNA1C protein (p.Met575Leu). This variant is present in population databases (no rsID available, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 1057413). 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 CACNA1C 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.
Ambry Genetics RCV003298589 SCV004005079 uncertain significance Cardiovascular phenotype 2023-05-05 criteria provided, single submitter clinical testing The p.M575L variant (also known as c.1723A>T), located in coding exon 13 of the CACNA1C gene, results from an A to T substitution at nucleotide position 1723. The methionine at codon 575 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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