ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1085del (p.Val362fs)

dbSNP: rs1555515739
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen CDH1 Variant Curation Expert Panel RCV003328419 SCV000864587 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-29 reviewed by expert panel curation The c.1085delT (p.Val362Glyfs*31) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_Supporting). The variant is absent in the gnomAD cohort (PM2_Supporting; http://gnomad.broadinstitute.org). This variant has been reported in at least one family meeting HDGC clinical criteria (PS4_Supporting; SCV000669065.1). 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 (Variant Interpretation Guidelines Version 3.1): PVS1, PM2_Supporting, PS4_Supporting, PM5_Supporting.
Ambry Genetics RCV000563263 SCV000669065 pathogenic Hereditary cancer-predisposing syndrome 2022-08-05 criteria provided, single submitter clinical testing The c.1085delT pathogenic mutation, located in coding exon 8 of the CDH1 gene, results from a deletion of one nucleotide at nucleotide position 1085, causing a translational frameshift with a predicted alternate stop codon (p.V362Gfs*31). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000736288 SCV003225312 pathogenic Hereditary diffuse gastric adenocarcinoma 2021-12-02 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: 483264). 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.Val362Glyfs*31) 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).

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