Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001754430 | SCV001987563 | uncertain significance | not provided | 2021-03-31 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function |
Center for Genomics, |
RCV003224577 | SCV003920551 | uncertain significance | Arrhythmogenic right ventricular dysplasia 1; Rienhoff syndrome | 2021-03-30 | criteria provided, single submitter | clinical testing | TGFB3 NM_003239.4 exon 1 p.Arg87Met (c.260G>T): This variant has not been reported in the literature, but it is present in 1/33582 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
Prevention |
RCV003407783 | SCV004106630 | uncertain significance | TGFB3-related disorder | 2022-12-26 | criteria provided, single submitter | clinical testing | The TGFB3 c.260G>T variant is predicted to result in the amino acid substitution p.Arg87Met. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/14-76446977-C-A). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Labcorp Genetics |
RCV005057560 | SCV005703716 | uncertain significance | Rienhoff syndrome | 2024-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 87 of the TGFB3 protein (p.Arg87Met). This variant is present in population databases (no rsID available, gnomAD 0.003%). 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: 1302541). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt TGFB3 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. |