Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001216821 | SCV001388634 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2020-02-11 | 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 been observed in an individual affected with hereditary diffuse gastric cancer (PMID: 28688938). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Gln23*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. |
Ambry Genetics | RCV002365978 | SCV002661842 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-04-30 | criteria provided, single submitter | clinical testing | The p.Q23* pathogenic mutation (also known as c.67C>T), located in coding exon 2 of the CDH1 gene, results from a C to T substitution at nucleotide position 67. This changes the amino acid from a glutamine to a stop codon within coding exon 2. This alteration was identified in an individual whose personal and/or family history met clinical criteria for a diagnosis of hereditary diffuse gastric cancer (Mi EZ et al. Gastrointest Endosc. 2018 02;87:408-418). This variant was also identified in 1/292 individuals with breast cancer (Xie Y et al. Clin Genet. 2018 Jan;93:41-51). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
European Reference Network on Genetic Tumour Risk Syndromes |
RCV001216821 | SCV003926904 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PVS1; PS4_Supporting; PM2 (PMID: 30311375) |
Myriad Genetics, |
RCV001216821 | SCV004043422 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2023-06-08 | 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. |