Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000804491 | SCV000944402 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2021-10-12 | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant has not been reported in the literature in individuals affected with CDH1-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces alanine with threonine at codon 10 of the CDH1 protein (p.Ala10Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. |
Ambry Genetics | RCV002440707 | SCV002750900 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-03 | criteria provided, single submitter | clinical testing | The p.A10T variant (also known as c.28G>A), located in coding exon 1 of the CDH1 gene, results from a G to A substitution at nucleotide position 28. The alanine at codon 10 is replaced by threonine, an amino acid with similar properties. This amino acid position is not well conserved on limited sequence alignment. 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. |
Baylor Genetics | RCV004569614 | SCV005060115 | uncertain significance | Familial cancer of breast | 2023-12-22 | criteria provided, single submitter | clinical testing |