ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.233G>A (p.Gly78Asp)

gnomAD frequency: 0.00001  dbSNP: rs587781404
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129255 SCV000184014 uncertain significance Hereditary cancer-predisposing syndrome 2023-05-24 criteria provided, single submitter clinical testing The p.G78D variant (also known as c.233G>A), located in coding exon 3 of the CDH1 gene, results from a G to A substitution at nucleotide position 233. The glycine at codon 78 is replaced by aspartic acid, an amino acid with similar properties. This alteration has been reported in 1/1197 individuals from Greece, Romania, and Turkey undergoing evaluation for inherited cancer predisposition (Tsaousis GN et al. BMC Cancer, 2019 Jun;19:535). In addition, this alteration was identified in an individual who had a family history of breast cancer (Garcia-Pelaez J et al. Lancet Oncol, 2023 Jan;24:91-106). This alteration was not observed in 7,051 unselected female breast cancer patients, in 11,241 female controls, or in 53 unselected male breast cancer patients, though was observed in 1/12,490 male controls of Japanese ancestry (Momozawa Y et al. Nat Commun, 2018 Oct;9:4083). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000230648 SCV000288463 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-08-30 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 78 of the CDH1 protein (p.Gly78Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of CDH1-related conditions (PMID: 31159747). ClinVar contains an entry for this variant (Variation ID: 140968). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
PreventionGenetics, part of Exact Sciences RCV000679570 SCV000806658 uncertain significance not provided 2017-02-20 criteria provided, single submitter clinical testing
GeneKor MSA RCV000129255 SCV000821971 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
European Reference Network on Genetic Tumour Risk Syndromes (ERN-GENTURIS), i3s - Instituto de Investigação e Inovação em Saúde, University of Porto RCV000230648 SCV003927007 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PM2 (PMID: 30311375)

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