ClinVar Miner

Submissions for variant NM_004360.5(CDH1):c.2332G>A (p.Ala778Thr)

gnomAD frequency: 0.00001  dbSNP: rs777078601
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000233980 SCV000288461 uncertain significance Hereditary diffuse gastric adenocarcinoma 2024-01-14 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 778 of the CDH1 protein (p.Ala778Thr). This variant is present in population databases (rs777078601, gnomAD 0.003%). This missense change has been observed in individual(s) with breast cancer (PMID: 28580595). ClinVar contains an entry for this variant (Variation ID: 239893). 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 disruptive. 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.
Ambry Genetics RCV000562000 SCV000666334 uncertain significance Hereditary cancer-predisposing syndrome 2024-04-16 criteria provided, single submitter clinical testing The p.A778T variant (also known as c.2332G>A), located in coding exon 15 of the CDH1 gene, results from a G to A substitution at nucleotide position 2332. The alanine at codon 778 is replaced by threonine, an amino acid with similar properties. This variant has been reported in several individuals with breast cancer (Xie Y et al. Clin Genet, 2018 Jan;93:41-51; Garcia-Pelaez J et al. Lancet Oncol, 2023 Jan;24:91-106). This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Counsyl RCV000233980 SCV000784835 uncertain significance Hereditary diffuse gastric adenocarcinoma 2016-12-21 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000562000 SCV000908764 uncertain significance Hereditary cancer-predisposing syndrome 2020-06-11 criteria provided, single submitter clinical testing This missense variant replaces alanine with threonine at codon 778 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with breast cancer in the literature (PMID: 28580595). This variant has been identified in 2/251448 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV002247674 SCV002518042 uncertain significance not specified 2022-05-04 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 RCV000233980 SCV003926928 uncertain significance Hereditary diffuse gastric adenocarcinoma 2022-08-01 criteria provided, single submitter clinical testing PM2 (PMID: 30311375)
Myriad Genetics, Inc. RCV000233980 SCV004019555 uncertain significance Hereditary diffuse gastric adenocarcinoma 2023-03-03 criteria provided, single submitter clinical testing This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk.
Baylor Genetics RCV004567740 SCV005060117 uncertain significance Familial cancer of breast 2023-12-18 criteria provided, single submitter clinical testing

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