ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.1097C>T (p.Thr366Met) (rs1429990170)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000658225 SCV000779996 uncertain significance not provided 2018-05-21 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1C gene. The T366M variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The T366M 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. In-silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. However, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Invitae RCV000697997 SCV000826635 uncertain significance Long QT syndrome 2018-02-12 criteria provided, single submitter clinical testing This sequence change replaces threonine with methionine at codon 366 of the CACNA1C protein (p.Thr366Met). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CACNA1C-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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