Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000228242 | SCV000289195 | uncertain significance | Gastrointestinal stromal tumor | 2024-02-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 979 of the PDGFRA protein (p.Arg979Cys). This variant is present in population databases (rs587778597, gnomAD 0.01%). This missense change has been observed in individual(s) with breast cancer (PMID: 24969172). ClinVar contains an entry for this variant (Variation ID: 135019). 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) performed at Invitae indicates that this missense variant is not expected to disrupt PDGFRA protein function with a negative predictive value of 80%. 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. |
Ambry Genetics | RCV002433614 | SCV002747798 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-11-25 | criteria provided, single submitter | clinical testing | The p.R979C variant (also known as c.2935C>T), located in coding exon 21 of the PDGFRA gene, results from a C to T substitution at nucleotide position 2935. The arginine at codon 979 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration was identified in one individual from a BRCA1/2-negative familial breast cancer kindred who underwent whole exome sequencing (Wen H et al. BMC Cancer 2014 Jun;14:470). This amino acid position is highly 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. |
ITMI | RCV000121788 | SCV000085986 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |