Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000621806 | SCV000738107 | uncertain significance | Cardiovascular phenotype | 2020-11-24 | criteria provided, single submitter | clinical testing | The p.H1943Y variant (also known as c.5827C>T), located in coding exon 46 of the CACNA1C gene, results from a C to T substitution at nucleotide position 5827. The histidine at codon 1943 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001347110 | SCV001541355 | uncertain significance | Long QT syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | 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. 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"). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1943 of the CACNA1C protein (p.His1943Tyr). This variant is present in population databases (rs200666365, gnomAD 0.004%). 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: 519485). |