ClinVar Miner

Submissions for variant NM_000719.7(CACNA1C):c.4773G>T (p.Lys1591Asn)

dbSNP: rs786205763
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000170811 SCV000223366 uncertain significance not provided 2019-08-15 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance but additional evidence is not available (ClinVar Variant ID# 190673; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect
Invitae RCV000798404 SCV000938021 uncertain significance Long QT syndrome 2023-08-29 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 1591 of the CACNA1C protein (p.Lys1591Asn). This variant is not present in population databases (gnomAD no frequency). 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: 190673). 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 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 RCV002336393 SCV002634723 uncertain significance Cardiovascular phenotype 2019-03-25 criteria provided, single submitter clinical testing The p.K1591N variant (also known as c.4773G>T), located in coding exon 39 of the CACNA1C gene, results from a G to T substitution at nucleotide position 4773. The lysine at codon 1591 is replaced by asparagine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV002498855 SCV002812706 uncertain significance Timothy syndrome; Brugada syndrome 3; Long qt syndrome 8 2021-08-23 criteria provided, single submitter clinical testing

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