Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV003526240 | SCV004315174 | uncertain significance | Gastrointestinal stromal tumor | 2023-08-28 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDGFRA protein function. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 583 of the PDGFRA protein (p.Asp583Gly). |
Ambry Genetics | RCV004943111 | SCV005471126 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-11-20 | criteria provided, single submitter | clinical testing | The p.D583G variant (also known as c.1748A>G), located in coding exon 11 of the PDGFRA gene, results from an A to G substitution at nucleotide position 1748. The aspartic acid at codon 583 is replaced by glycine, an amino acid with similar properties. This variant was observed in the tumor cells of a 53 year old patient with a GIST (Wu Y et al. World J Surg Oncol, 2023 Apr;21:138). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |