Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000633841 | SCV000755114 | uncertain significance | Gastrointestinal stromal tumor | 2022-04-23 | criteria provided, single submitter | clinical testing | 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. This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 425 of the PDGFRA protein (p.His425Gln). 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: 528619). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 | RCV004944036 | SCV005471063 | uncertain significance | Hereditary cancer-predisposing syndrome | 2024-07-27 | criteria provided, single submitter | clinical testing | The p.H425Q variant (also known as c.1275T>G), located in coding exon 8 of the PDGFRA gene, results from a T to G substitution at nucleotide position 1275. The histidine at codon 425 is replaced by glutamine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |