ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.283C>T (p.Gln95Ter)

dbSNP: rs781409616
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328400 SCV000864615 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-29 reviewed by expert panel curation The c.283C>T (p.Gln95*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is present in <1/100,000 alleles in the gnomAD cohort. (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least 2 families meeting HDGC clinical criteria (PS4_Moderate; PMID: 17545690, internal laboratory contributor). In summary, 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Moderate, PM5_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000546548 SCV000637817 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-12-02 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln95*) 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 present in population databases (rs781409616, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with gastric cancer and gastric, breast, and colon cancer (PMID: 11434599, 17545690, 21271559, 23709761, 26484312). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 463775). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health RCV001805167 SCV002052264 pathogenic Hereditary cancer-predisposing syndrome 2021-06-07 criteria provided, single submitter clinical testing This variant changes 1 nucleotide in exon 3 of the CDH1 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with hereditary diffuse gastic cancer (HDGC) in the literature and was observed to co-segregate with HDGC in one family (PMID: 11434599, 17545690, 23709761). The variant has also been observed in breast and colorectal cancer cases (PMID: 21271559, 26484312). This variant has been identified in 1/251330 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics RCV001805167 SCV002752662 pathogenic Hereditary cancer-predisposing syndrome 2020-01-14 criteria provided, single submitter clinical testing The p.Q95* pathogenic mutation (also known as c.283C>T), located in coding exon 3 of the CDH1 gene, results from a C to T substitution at nucleotide position 283. This changes the amino acid from a glutamine to a stop codon within coding exon 3. This alteration has been reported in several hereditary diffuse gastric cancer and/or lobular breast cancer families (Dussaulx-Garin L et al. Eur J Gastroenterol Hepatol, 2001 Jun;13:711-5; Xie ZM et al. Cancer, 2011 Jul;117:3112-7; Benusiglio PR et al. J. Med. Genet., 2013 Jul;50:486-9). 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 (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV000546548 SCV003927014 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PVS1; PS4_Moderate; PM2 (PMID: 30311375)
Myriad Genetics, Inc. RCV000546548 SCV004043344 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.
Mayo Clinic Laboratories, Mayo Clinic RCV004791544 SCV005414352 pathogenic not provided 2024-05-17 criteria provided, single submitter clinical testing PM2, PM5_supporting, PS4_moderate, PVS1

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.