Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003328150 | SCV001142249 | pathogenic | CDH1-related diffuse gastric and lobular breast cancer syndrome | 2023-08-04 | reviewed by expert panel | curation | The c.781G>T (p.Glu261Ter) variant is predicted to result in a premature stop codon that leads to nonsense mediate decay (PVS1 and PM5_supporting). The variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). Therefore, this variant meets criteria to be classified as pathogenic based on the ACMG/AMP criteria applied as specified by the CDH1 Variant Curation Expert Panel (CDH1 VCEP specifications version 3.1): PVS1, PM2_supporting, PM5_supporting. |
Invitae | RCV000991090 | SCV002147714 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2021-04-11 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu261*) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDH1 are known to be pathogenic (PMID: 15235021, 20373070). This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. This variant has been observed in individual(s) with lobular breast cancer (PMID: 9744472). ClinVar contains an entry for this variant (Variation ID: 12234). |
Ambry Genetics | RCV002408458 | SCV002673353 | pathogenic | Hereditary cancer-predisposing syndrome | 2020-09-09 | criteria provided, single submitter | clinical testing | The p.E261* pathogenic mutation (also known as c.781G>T), located in coding exon 6 of the CDH1 gene, results from a G to T substitution at nucleotide position 781. This changes the amino acid from a glutamic acid to a stop codon within coding exon 6. This alteration was previously detected in a patient with lobular breast cancer (Berx G et al. EMBO J., 1995 Dec;14:6107-15). 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 |
RCV000991090 | SCV003926688 | pathogenic | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PVS1; PS4_Moderate; PM2 (PMID: 30311375) |
OMIM | RCV000013021 | SCV000033266 | pathogenic | Breast lobular carcinoma | 1995-12-15 | no assertion criteria provided | literature only | |
Laboratory for Genotyping Development, |
RCV003162242 | SCV002758156 | pathogenic | Gastric cancer | 2021-07-01 | no assertion criteria provided | research |