Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001299478 | SCV001488570 | uncertain significance | Aortic valve disease 2 | 2022-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 482 of the SMAD6 protein (p.Thr482Ser). 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 SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 539112). 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 SMAD6 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 | RCV004025755 | SCV005023202 | uncertain significance | Inborn genetic diseases | 2024-03-13 | criteria provided, single submitter | clinical testing | The p.T482S variant (also known as c.1445C>G), located in coding exon 4 of the SMAD6 gene, results from a C to G substitution at nucleotide position 1445. The threonine at codon 482 is replaced by serine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. |