Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000573781 | SCV000661634 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-11-11 | criteria provided, single submitter | clinical testing | The p.D538Y variant (also known as c.1612G>T), located in coding exon 11 of the CDH1 gene, results from a G to T substitution at nucleotide position 1612. The aspartic acid at codon 538 is replaced by tyrosine, an amino acid with highly dissimilar properties. This amino acid position is not well conserved in available vertebrate species. 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. |
Prevention |
RCV000679563 | SCV000806639 | uncertain significance | not provided | 2017-11-27 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001325307 | SCV001516293 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2023-06-27 | 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: 479491). This variant has not been reported in the literature in individuals affected with CDH1-related conditions. This variant is present in population databases (rs756154596, gnomAD 0.006%). This sequence change replaces aspartic acid, which is acidic and polar, with tyrosine, which is neutral and polar, at codon 538 of the CDH1 protein (p.Asp538Tyr). |
Baylor Genetics | RCV003459281 | SCV004215626 | uncertain significance | Familial cancer of breast | 2023-10-06 | criteria provided, single submitter | clinical testing |