ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.842C>T (p.Thr281Met)

gnomAD frequency: 0.00003  dbSNP: rs770343276
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000232711 SCV000289225 uncertain significance Gastrointestinal stromal tumor 2023-12-30 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 281 of the PDGFRA protein (p.Thr281Met). This variant is present in population databases (rs770343276, gnomAD 0.006%). 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: 240363). 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 RCV002444904 SCV002680716 uncertain significance Hereditary cancer-predisposing syndrome 2022-09-28 criteria provided, single submitter clinical testing The p.T281M variant (also known as c.842C>T), located in coding exon 5 of the PDGFRA gene, results from a C to T substitution at nucleotide position 842. The threonine at codon 281 is replaced by methionine, 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.
GeneDx RCV002509330 SCV002818729 uncertain significance not provided 2022-07-07 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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