Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000568722 | SCV000666298 | uncertain significance | Hereditary cancer-predisposing syndrome | 2016-04-05 | criteria provided, single submitter | clinical testing | The p.V660E variant (also known as c.1979T>A), located in coding exon 13 of the CDH1 gene, results from a T to A substitution at nucleotide position 1979. The valine at codon 660 is replaced by glutamic acid, an amino acid with dissimilar properties. 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. In the ESP, this variant was not observed in 6498 samples (12996 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. 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 |
RCV002528008 | SCV003302358 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-01-26 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 481684). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 660 of the CDH1 protein (p.Val660Glu). |
| Baylor Genetics | RCV003459324 | SCV004215596 | uncertain significance | Familial cancer of breast | 2023-10-31 | criteria provided, single submitter | clinical testing |