Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000467030 | SCV000546603 | uncertain significance | Gastrointestinal stromal tumor | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 323 of the PDGFRA protein (p.Gln323Glu). This variant is present in population databases (rs138296072, gnomAD 0.02%). 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: 407405). 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. |
Ambry Genetics | RCV001019616 | SCV001180997 | benign | Hereditary cancer-predisposing syndrome | 2024-10-28 | criteria provided, single submitter | clinical testing | This alteration is classified as 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. |
Prevention |
RCV003418171 | SCV004113608 | uncertain significance | PDGFRA-related disorder | 2023-01-11 | criteria provided, single submitter | clinical testing | The PDGFRA c.967C>G variant is predicted to result in the amino acid substitution p.Gln323Glu. This variant is reported in 0.020% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55133754-C-G) and is interpreted as a variant of uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/407405/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Gene |
RCV005001053 | SCV005626712 | uncertain significance | not provided | 2024-07-12 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |