Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000464498 | SCV000545446 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-08-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 415 of the CDH1 protein (p.Ile415Val). This variant is present in population databases (no rsID available, gnomAD 0.007%). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). ClinVar contains an entry for this variant (Variation ID: 406656). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV000562614 | SCV000661626 | likely benign | Hereditary cancer-predisposing syndrome | 2016-12-22 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Color Diagnostics, |
RCV000562614 | SCV001341167 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-07-25 | criteria provided, single submitter | clinical testing | This missense variant replaces isoleucine with valine at codon 415 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 been identified in 1/31392 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. |
Gene |
RCV001764383 | SCV002008946 | uncertain significance | not provided | 2023-07-13 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in individuals with breast cancer, but also in unaffected controls (Momozawa et al., 2018); This variant is associated with the following publications: (PMID: 15235021, 22850631, 30287823) |