Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000573208 | SCV000666319 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-07-01 | criteria provided, single submitter | clinical testing | The p.V660A variant (also known as c.1979T>C), located in coding exon 13 of the CDH1 gene, results from a T to C substitution at nucleotide position 1979. The valine at codon 660 is replaced by alanine, an amino acid with similar properties. This amino acid position is poorly 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. |
| Labcorp Genetics |
RCV000820444 | SCV000961157 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2024-01-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 660 of the CDH1 protein (p.Val660Ala). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 481696). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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. |
| Color Diagnostics, |
RCV000573208 | SCV004360509 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-06 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with alanine at codon 660 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |