Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001897924 | SCV002166075 | uncertain significance | Aortic valve disease 2 | 2023-03-18 | 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1389430). 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 glycine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 33 of the SMAD6 protein (p.Gly33Cys). |
| Ambry Genetics | RCV004671499 | SCV005167184 | uncertain significance | Inborn genetic diseases | 2024-04-04 | criteria provided, single submitter | clinical testing | The p.G33C variant (also known as c.97G>T), located in coding exon 1 of the SMAD6 gene, results from a G to T substitution at nucleotide position 97. The glycine at codon 33 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. |