Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002428047 | SCV002728853 | uncertain significance | Cardiovascular phenotype | 2024-04-13 | criteria provided, single submitter | clinical testing | The p.A740V variant (also known as c.2219C>T), located in coding exon 16 of the VCL gene, results from a C to T substitution at nucleotide position 2219. The alanine at codon 740 is replaced by valine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. The evidence for this gene-disease relationship is limited; therefore, the clinical significance of this alteration is unclear. |
| Labcorp Genetics |
RCV003098728 | SCV003334695 | uncertain significance | Dilated cardiomyopathy 1W | 2022-11-04 | criteria provided, single submitter | clinical testing | This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 740 of the VCL protein (p.Ala740Val). This variant is present in population databases (rs775403638, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with VCL-related conditions. 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: "Not Available"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Not Available"). 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. |