ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.1421C>T (p.Thr474Met)

gnomAD frequency: 0.00001  dbSNP: rs751618661
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000633720 SCV000754993 uncertain significance Gastrointestinal stromal tumor 2023-11-03 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 474 of the PDGFRA protein (p.Thr474Met). This variant is present in population databases (rs751618661, gnomAD 0.006%). This missense change has been observed in individual(s) with non-syndromic cleft palate (PMID: 22473090). This variant is also known as c.1420C>T. ClinVar contains an entry for this variant (Variation ID: 528499). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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.
Ambry Genetics RCV002388020 SCV002698582 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-24 criteria provided, single submitter clinical testing The p.T474M variant (also known as c.1421C>T), located in coding exon 9 of the PDGFRA gene, results from a C to T substitution at nucleotide position 1421. The threonine at codon 474 is replaced by methionine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. 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.

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