Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000246740 | SCV000318867 | uncertain significance | Cardiovascular phenotype | 2013-07-11 | criteria provided, single submitter | clinical testing | ​The p.E1302K (also known as c.3904G>A) variant is located in coding exon 30 of the CACNA1C gene. This variant results from a G to A substitution at nucleotide position 3904. The glutamate at codon 1302 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved on sequence alignment. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. This variant is predicted to be probably damaging by PolyPhen, but tolerated by SIFT in silico analyses. Since supporting evidence is limited at this time, the clinical significance of p.E1302K remains unclear. |
Invitae | RCV001364253 | SCV001560388 | uncertain significance | Long QT syndrome | 2020-08-06 | criteria provided, single submitter | clinical testing | Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; 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. This variant has not been reported in the literature in individuals with CACNA1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 263682). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with lysine at codon 1302 of the CACNA1C protein (p.Glu1302Lys). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and lysine. |