Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001050568 | SCV001214683 | uncertain significance | Gastrointestinal stromal tumor | 2019-10-30 | 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 504 of the PDGFRA protein (p.Lys504Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid. |
| Ambry Genetics | RCV003307854 | SCV004000110 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-22 | criteria provided, single submitter | clinical testing | The p.K504E variant (also known as c.1510A>G), located in coding exon 9 of the PDGFRA gene, results from an A to G substitution at nucleotide position 1510. The lysine at codon 504 is replaced by glutamic acid, an amino acid with similar properties. This amino acid position is conserved. 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. |