ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.376_382dup (p.His128fs)

dbSNP: rs1567501500
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328456 SCV001244346 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-04 reviewed by expert panel curation The c.369_375CCGCCCC[3] (p.His128Profs*42) 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000687705 SCV000815290 pathogenic Hereditary diffuse gastric adenocarcinoma 2018-04-19 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 sequence change creates a premature translational stop signal (p.His128Profs*42) in the CDH1 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDH1-related disease.
Ambry Genetics RCV002343438 SCV002623044 pathogenic Hereditary cancer-predisposing syndrome 2020-11-16 criteria provided, single submitter clinical testing The c.376_382dupCCGCCCC pathogenic mutation, located in coding exon 3 of the CDH1 gene, results from a duplication of CCGCCCC at nucleotide position 376, causing a translational frameshift with a predicted alternate stop codon (p.H128Pfs*42). 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.
Myriad Genetics, Inc. RCV000687705 SCV004044447 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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