Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000465785 | SCV000546591 | uncertain significance | Gastrointestinal stromal tumor | 2020-12-23 | 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 PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 407396). This variant is not present in population databases (ExAC no frequency). This sequence change replaces valine with isoleucine at codon 469 of the PDGFRA protein (p.Val469Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. |
| Ambry Genetics | RCV002393107 | SCV002699183 | likely benign | Hereditary cancer-predisposing syndrome | 2021-10-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |