Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000799652 | SCV000939325 | uncertain significance | Aortic valve disease 2 | 2018-11-07 | 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 (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SMAD6-related disease. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate insufficient coverage at this position in the ExAC database. This sequence change replaces proline with leucine at codon 138 of the SMAD6 protein (p.Pro138Leu). The proline residue is moderately conserved and there is a moderate physicochemical difference between proline and leucine. |
| Ambry Genetics | RCV002332622 | SCV002629363 | uncertain significance | Inborn genetic diseases | 2021-08-22 | criteria provided, single submitter | clinical testing | The p.P138L variant (also known as c.413C>T), located in coding exon 1 of the SMAD6 gene, results from a C to T substitution at nucleotide position 413. The proline at codon 138 is replaced by leucine, an amino acid with similar 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. |