Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV002370835 | SCV002672341 | uncertain significance | Inborn genetic diseases | 2022-01-02 | criteria provided, single submitter | clinical testing | The p.E24G variant (also known as c.71A>G), located in coding exon 1 of the SMAD6 gene, results from an A to G substitution at nucleotide position 71. The glutamic acid at codon 24 is replaced by glycine, 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. |
Labcorp Genetics |
RCV003098499 | SCV003447389 | uncertain significance | Aortic valve disease 2 | 2023-02-14 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs752328938, gnomAD 0.006%). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 24 of the SMAD6 protein (p.Glu24Gly). This variant has not been reported in the literature in individuals affected with SMAD6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1757641). 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. 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. |