Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001193904 | SCV001363072 | likely pathogenic | Hereditary diffuse gastric adenocarcinoma | 2021-12-10 | criteria provided, single submitter | clinical testing | Variant summary: CDH1 c.103G>T (p.Glu35X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 156712 control chromosomes (gnomAD). c.103G>T has been reported in the literature as a somatic variant in individuals affected with invasive lobular carcinoma (Sakr_2016), and plasmacytoid variant bladder cancer (Al-Ahmadie_2016). These reports do not provide unequivocal conclusions about the germline association of the variant with Hereditary Diffuse Gastric Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
Labcorp Genetics |
RCV001193904 | SCV001389987 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2019-07-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant has not been reported in the literature in individuals with CDH1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu35*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. |
Myriad Genetics, |
RCV001193904 | SCV005403965 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2024-07-23 | criteria provided, single submitter | clinical testing | This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation. |