Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
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, |
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 |
RCV000233980 | SCV003926928 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-01 | criteria provided, single submitter | clinical testing | PM2 (PMID: 30311375) |
Myriad Genetics, |
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 |