Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000568330 | SCV000661656 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-12-14 | criteria provided, single submitter | clinical testing | The p.E208K variant (also known as c.622G>A), located in coding exon 5 of the CDH1 gene, results from a G to A substitution at nucleotide position 622. The glutamic acid at codon 208 is replaced by lysine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
Color Diagnostics, |
RCV000568330 | SCV000908814 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-05 | criteria provided, single submitter | clinical testing | This missense variant replaces glutamic acid with lysine at codon 208 of the CDH1 protein. To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with CDH1-related disorders in the literature. This variant has been identified in 1/251152 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. |
Labcorp Genetics |
RCV001038894 | SCV001202394 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-08-03 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 479506). 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 replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 208 of the CDH1 protein (p.Glu208Lys). |
Sema4, |
RCV000568330 | SCV002529198 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-04-12 | criteria provided, single submitter | curation |