ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2095C>T (p.Gln699Ter)

dbSNP: rs121964874
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328152 SCV001365436 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-25 reviewed by expert panel curation The c.2095C>T (p.Gln699Ter) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). This variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; PMID: 9537325). 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_Supporting, PM5_Supporting.
Labcorp Genetics (formerly Invitae), Labcorp RCV000013024 SCV002234263 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-07-22 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 12237). This premature translational stop signal has been observed in individual(s) with diffuse gastric cancer (PMID: 9537325). This sequence change creates a premature translational stop signal (p.Gln699*) 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).
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV000013024 SCV003926890 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PVS1; PS4_Supporting; PM2 (PMID: 30311375)
Myriad Genetics, Inc. RCV000013024 SCV004044510 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-15 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.
OMIM RCV004579520 SCV000033269 pathogenic DIFFUSE GASTRIC AND LOBULAR BREAST CANCER SYNDROME 1998-03-26 no assertion criteria provided literature only

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