Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002333310 | SCV002628079 | uncertain significance | Inborn genetic diseases | 2023-12-31 | criteria provided, single submitter | clinical testing | The p.R139W variant (also known as c.415C>T), located in coding exon 1 of the SMAD6 gene, results from a C to T substitution at nucleotide position 415. The arginine at codon 139 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is conserved. 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. |
| Labcorp Genetics |
RCV003094551 | SCV002937018 | uncertain significance | Aortic valve disease 2 | 2022-12-31 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. This variant is present in population databases (rs554746292, gnomAD 0.05%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 139 of the SMAD6 protein (p.Arg139Trp). ClinVar contains an entry for this variant (Variation ID: 1738331). 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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). |