Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001931799 | SCV002211791 | uncertain significance | Aortic valve disease 2 | 2021-09-08 | 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. Experimental studies have shown that this missense change affects SMAD6 function (PMID: 32499606). 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 disruptive. This missense change has been observed in individual(s) with craniosynostosis (PMID: 32499606). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 473 of the SMAD6 protein (p.Gly473Arg). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and arginine. |