ClinVar Miner

Submissions for variant NM_006206.6(PDGFRA):c.1822G>A (p.Val608Ile)

gnomAD frequency: 0.00002  dbSNP: rs138740193
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000457211 SCV000546630 uncertain significance Gastrointestinal stromal tumor 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 608 of the PDGFRA protein (p.Val608Ile). This variant is present in population databases (rs138740193, gnomAD 0.009%). 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: 407429). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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.
GeneDx RCV003329280 SCV004036884 uncertain significance not provided 2023-06-25 criteria provided, single submitter clinical testing 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
PreventionGenetics, part of Exact Sciences RCV003418172 SCV004118663 uncertain significance PDGFRA-related disorder 2023-04-20 criteria provided, single submitter clinical testing The PDGFRA c.1822G>A variant is predicted to result in the amino acid substitution p.Val608Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55143590-G-A). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/407429/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Baylor Genetics RCV003476052 SCV004200934 uncertain significance Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal 2023-08-14 criteria provided, single submitter clinical testing
Ambry Genetics RCV004943877 SCV005470984 likely benign Hereditary cancer-predisposing syndrome 2024-08-20 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

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