Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001215818 | SCV001387581 | uncertain significance | Aortic valve disease 2 | 2019-06-17 | 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces valine with isoleucine at codon 426 of the SMAD6 protein (p.Val426Ile). The valine residue is moderately conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs376580255, ExAC 0.002%). This variant has not been reported in the literature in individuals with SMAD6-related conditions. |
| Ambry Genetics | RCV004033979 | SCV005023708 | uncertain significance | Inborn genetic diseases | 2023-12-12 | criteria provided, single submitter | clinical testing | The p.V426I variant (also known as c.1276G>A), located in coding exon 4 of the SMAD6 gene, results from a G to A substitution at nucleotide position 1276. The valine at codon 426 is replaced by isoleucine, an amino acid with highly 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. |