Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166059 | SCV000216821 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-02-08 | criteria provided, single submitter | clinical testing | The p.V328M variant (also known as c.982G>A), located in coding exon 7 of the CDH1 gene, results from a G to A substitution at nucleotide position 982. The valine at codon 328 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this alteration remains unclear. |
| Gene |
RCV000478474 | SCV000564834 | uncertain significance | not provided | 2015-02-16 | criteria provided, single submitter | clinical testing | This variant is denoted CDH1 c.982G>A at the cDNA level, p.Val328Met (V328M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. CDH1 Val328Met was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. CDH1 Val328Met occurs at a position that is conserved across species and is located in the cadherin 2 domain (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether CDH1 Val328Met is pathogenic or benign. We consider it to be a variant of uncertain significance. |
| Labcorp Genetics |
RCV000686762 | SCV000814295 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-02-19 | 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 sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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"). ClinVar contains an entry for this variant (Variation ID: 186460). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (rs754228872, gnomAD 0.003%). This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 328 of the CDH1 protein (p.Val328Met). |
| Color Diagnostics, |
RCV000166059 | SCV004360463 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-31 | criteria provided, single submitter | clinical testing | This missense variant replaces valine with methionine at codon 328 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 CDH1-related disorders in the literature. This variant has been identified in 1/251360 chromosomes 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. |
| Baylor Genetics | RCV004567293 | SCV005060092 | uncertain significance | Familial cancer of breast | 2024-02-05 | criteria provided, single submitter | clinical testing |