Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000694495 | SCV000822944 | uncertain significance | Gastrointestinal stromal tumor | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with histidine, which is basic and polar, at codon 353 of the PDGFRA protein (p.Asn353His). This variant is present in population databases (rs139103850, 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: 135027). 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 | RCV002399488 | SCV002712488 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-14 | criteria provided, single submitter | clinical testing | The p.N353H variant (also known as c.1057A>C), located in coding exon 6 of the PDGFRA gene, results from an A to C substitution at nucleotide position 1057. The asparagine at codon 353 is replaced by histidine, an amino acid with similar properties. This variant was identified in a cohort of 681 ancestrally diverse, healthy subjects (Bodian DL et al. PLoS ONE, 2014 Apr;9:e94554). This amino acid position is well 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. |
Gene |
RCV003236780 | SCV003935379 | uncertain significance | not provided | 2022-12-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in healthy individuals undergoing whole genome sequencing (Bodian et al., 2014); This variant is associated with the following publications: (PMID: 24728327) |
Prevention |
RCV003407521 | SCV004107175 | uncertain significance | PDGFRA-related condition | 2023-08-18 | criteria provided, single submitter | clinical testing | The PDGFRA c.1057A>C variant is predicted to result in the amino acid substitution p.Asn353His. It has been reported in an individual from a genome sequencing cohort of healthy individuals (Table S1, Bodian et al. 2014. PubMed ID: 24728327). This variant is reported in 0.024% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/4-55133844-A-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/135027/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
St. |
RCV003444204 | SCV004171483 | uncertain significance | Polyps, multiple and recurrent inflammatory fibroid, gastrointestinal | 2023-10-18 | criteria provided, single submitter | clinical testing | The PDGFRA c.1057A>C (p.Asn353His) missense change has a maximum subpopulation frequency of 0.024% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with PDGFRA-related conditions. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
ITMI | RCV000121799 | SCV000085997 | not provided | not specified | 2013-09-19 | no assertion provided | reference population |