Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000216872 | SCV000275983 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.T217I variant (also known as c.650C>T), located in coding exon 5 of the CDH1 gene, results from a C to T substitution at nucleotide position 650. The threonine at codon 217 is replaced by isoleucine, 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 |
RCV001323284 | SCV001514192 | uncertain significance | Hereditary diffuse gastric adenocarcinoma | 2020-08-26 | 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with CDH1-related conditions. ClinVar contains an entry for this variant (Variation ID: 231975). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 217 of the CDH1 protein (p.Thr217Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
Baylor Genetics | RCV004567585 | SCV005060096 | uncertain significance | Familial cancer of breast | 2024-01-20 | criteria provided, single submitter | clinical testing |