Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000562032 | SCV000666311 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-07 | criteria provided, single submitter | clinical testing | The p.K816E variant (also known as c.2446A>G), located in coding exon 16 of the CDH1 gene, results from an A to G substitution at nucleotide position 2446. The lysine at codon 816 is replaced by glutamic acid, 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. |
Labcorp Genetics |
RCV002298674 | SCV002590511 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2022-08-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDH1-related conditions. 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 481691). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 816 of the CDH1 protein (p.Lys816Glu). |
Color Diagnostics, |
RCV000562032 | SCV004361273 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-12-13 | criteria provided, single submitter | clinical testing | This missense variant replaces lysine with glutamic acid at codon 816 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 not been identified 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. |