ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1064dup (p.Leu355fs)

dbSNP: rs1555515731
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001065791 SCV001230775 pathogenic Hereditary diffuse gastric adenocarcinoma 2022-02-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu355Phefs*13) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with diffuse gastric cancer (PMID: 15235021). ClinVar contains an entry for this variant (Variation ID: 859633). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV003160542 SCV003867764 pathogenic Hereditary cancer-predisposing syndrome 2023-02-24 criteria provided, single submitter clinical testing The c.1064dupT pathogenic mutation, located in coding exon 8 of the CDH1 gene, results from a duplication of T at nucleotide position 1064, causing a translational frameshift with a predicted alternate stop codon (p.L355Ffs*13). This alteration has been reported in an individual affected with diffuse gastric cancer (Brooks-Wilson AR et al. J Med Genet, 2004 Jul;41:508-17). This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Myriad Genetics, Inc. RCV001065791 SCV004045459 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-12 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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