Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001237718 | SCV001410491 | uncertain significance | Aortic valve disease 2 | 2019-11-02 | criteria provided, single submitter | clinical testing | 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: "Possibly Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with SMAD6-related conditions. This variant is present in population databases (rs372082813, ExAC 0.003%). This sequence change replaces proline with leucine at codon 278 of the SMAD6 protein (p.Pro278Leu). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and leucine. |
| Ambry Genetics | RCV002436932 | SCV002680547 | uncertain significance | Inborn genetic diseases | 2022-07-25 | criteria provided, single submitter | clinical testing | The p.P278L variant (also known as c.833C>T), located in coding exon 2 of the SMAD6 gene, results from a C to T substitution at nucleotide position 833. The proline at codon 278 is replaced by leucine, 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. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |