ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.1531C>T (p.Gln511Ter)

dbSNP: rs1131690810
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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 RCV003328371 SCV001365415 pathogenic CDH1-related diffuse gastric and lobular breast cancer syndrome 2023-08-25 reviewed by expert panel curation The c.1531C>T p.(Gln511*) variant is predicted to result in a premature stop codon that leads to a truncated or absent protein (PVS1, PM5_supporting). This variant is absent in the gnomAD cohort (PM2_supporting; http://gnomad.broadinstitute.org). The variant has been reported in at least two families meeting HDGC clinical criteria (PS4_moderate; PMID: 31600923 and SCV000580698.3). In summary, 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_moderate, PM5_supporting.
Ambry Genetics RCV000492683 SCV000580698 pathogenic Hereditary cancer-predisposing syndrome 2013-07-09 criteria provided, single submitter clinical testing ​The p.Q511X pathogenic mutation (also known as c.1531C>T), located in exon 10 of the CDH1 gene, results from a C to T substitution at nucleotide position 1531. This changes the amino acid from a glutamine to a stop codon within exon 10. Since premature stop codons are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Labcorp Genetics (formerly Invitae), Labcorp RCV000810270 SCV000950463 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-05-07 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: 428621). 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.Gln511*) 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. RCV000810270 SCV004045140 pathogenic Hereditary diffuse gastric adenocarcinoma 2023-06-14 criteria provided, single submitter clinical testing This variant is considered pathogenic. This variant creates a termination codon and is predicted to result in premature protein truncation.

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