ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1397_1398del (p.Leu466fs)

dbSNP: rs1597897893
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV000774142 SCV000907843 pathogenic Hereditary cancer-predisposing syndrome 2020-07-13 criteria provided, single submitter clinical testing This variant deletes 2 nucleotides in exon 10 of the CDH1 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with diffuse gastric cancer and breast cancer (PMID: 17221870, 17545690, 21271559). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of CDH1 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Ambry Genetics RCV000774142 SCV002697675 pathogenic Hereditary cancer-predisposing syndrome 2022-07-07 criteria provided, single submitter clinical testing The c.1397_1398delTC variant, located in coding exon 10 of the CDH1 gene, results from a deletion of two nucleotides at nucleotide positions 1397 to 1398, causing a translational frameshift with a predicted alternate stop codon (p.L466Hfs*16). This alteration has been observed in at least two families with a history of gastric cancer (at least one confirmed diffuse gastric cancer in each family) and breast cancer (Kaurah P et al. JAMA, 2007 Jun;297:2360-72; More H et al. Hum Mutat, 2007 Feb;28:203). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Of note, this alteration is also designated as c.1391_1392delTC (p.Leu472HisfsX481) in published 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. RCV003336179 SCV004044374 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-13 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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