ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.202del (p.Tyr68fs)

dbSNP: rs786202151
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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 RCV003328253 SCV001142264 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.202delT (p.Tyr68Ilefs*15) 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.
Ambry Genetics RCV000164820 SCV000215503 pathogenic Hereditary cancer-predisposing syndrome 2022-04-04 criteria provided, single submitter clinical testing The c.202delT pathogenic mutation, located in coding exon 3 of the CDH1 gene, results from a deletion of one nucleotide at nucleotide position 202, causing a translational frameshift with a predicted alternate stop codon (p.Y68Ifs*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.
GeneDx RCV000479654 SCV000569632 pathogenic not provided 2016-03-17 criteria provided, single submitter clinical testing This deletion of one nucleotide in CDH1 is denoted c.202delT at the cDNA level and p.Tyr68IlefsX15 (Y68IfsX15) at the protein level. The normal sequence, with the base that is deleted in braces, is AGCC[T]ATTT. The deletion causes a frameshift which changes a Tyrosine to an Isoleucine at codon 68, and creates a premature stop codon at position 15 of the new reading frame. Although this variant has not, to our knowledge, been reported in the literature, it is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. We consider this variant to be pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp RCV000685278 SCV000812755 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-03-05 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 185408). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr68Ilefs*15) 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).
Myriad Genetics, Inc. RCV000685278 SCV004043568 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-08 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a frameshift predicted to result in premature protein truncation.

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