Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Biesecker Lab/Clinical Genomics Section, |
RCV000172112 | SCV000051055 | uncertain significance | not provided | 2013-06-24 | criteria provided, single submitter | research | |
| Gene |
RCV000412926 | SCV000492327 | uncertain significance | not specified | 2016-12-06 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the TGFB3 gene. The R163W variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. This variant was not observed with any significant frequency both in the Exome Aggregation Consortium and in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R163W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position that is conserved across species. Furthermore, in silico analysis predicts this variant may be damaging to the protein structure/function. Nevertheless, no missense variants in nearby residues have been reported in the Human Gene Mutation Database in association with disease (Stenson et al., 2014).Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time. |
| Labcorp Genetics |
RCV002517659 | SCV000776803 | uncertain significance | Rienhoff syndrome | 2023-10-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 163 of the TGFB3 protein (p.Arg163Trp). This variant is present in population databases (rs142601521, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with TGFB3-related conditions. ClinVar contains an entry for this variant (Variation ID: 191779). 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 TGFB3 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 | RCV002336410 | SCV002638720 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2023-07-20 | criteria provided, single submitter | clinical testing | The p.R163W variant (also known as c.487C>T), located in coding exon 2 of the TGFB3 gene, results from a C to T substitution at nucleotide position 487. The arginine at codon 163 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in an aortopathy cohort; however, clinical details were limited (Renner S et al. Genet Med, 2019 Aug;21:1832-1841). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV002478553 | SCV002780838 | uncertain significance | Arrhythmogenic right ventricular dysplasia 1; Rienhoff syndrome | 2021-11-08 | criteria provided, single submitter | clinical testing |