Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003534646 | SCV000824337 | uncertain significance | Familial adenomatous polyposis 1 | 2018-03-10 | 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, 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 APC-related disease. This variant is present in population databases (rs773849124, ExAC 0.02%). This sequence change replaces valine with alanine at codon 915 of the APC protein (p.Val915Ala). The valine residue is moderately conserved and there is a small physicochemical difference between valine and alanine. |
| Ambry Genetics | RCV003338737 | SCV004059036 | likely benign | Hereditary cancer-predisposing syndrome | 2023-07-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
| Baylor Genetics | RCV002532333 | SCV004197609 | uncertain significance | Familial adenomatous polyposis 1 | 2023-10-27 | criteria provided, single submitter | clinical testing |