Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001960098 | SCV002214321 | uncertain significance | Aortic valve disease 2 | 2022-10-31 | 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: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 1433429). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 42 of the SMAD6 protein (p.Arg42Gln). |
| Ambry Genetics | RCV002425281 | SCV002678326 | uncertain significance | Inborn genetic diseases | 2022-01-26 | criteria provided, single submitter | clinical testing | The p.R42Q variant (also known as c.125G>A), located in coding exon 1 of the SMAD6 gene, results from a G to A substitution at nucleotide position 125. The arginine at codon 42 is replaced by glutamine, 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. |