Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002320451 | SCV002607477 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-12-15 | criteria provided, single submitter | clinical testing | The p.H1040Y variant (also known as c.3118C>T), located in coding exon 21 of the PDGFRA gene, results from a C to T substitution at nucleotide position 3118. The histidine at codon 1040 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003526127 | SCV004269061 | uncertain significance | Gastrointestinal stromal tumor | 2023-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 1040 of the PDGFRA protein (p.His1040Tyr). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PDGFRA-related conditions. ClinVar contains an entry for this variant (Variation ID: 1727819). 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. 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. |