Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001890664 | SCV002156930 | uncertain significance | Multiple congenital exostosis | 2021-03-28 | criteria provided, single submitter | clinical testing | This sequence change replaces tryptophan with arginine at codon 304 of the EXT1 protein (p.Trp304Arg). The tryptophan residue is highly conserved and there is a moderate physicochemical difference between tryptophan and arginine. This variant is not present in population databases (ExAC no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt EXT1 protein function. This variant has not been reported in the literature in individuals with EXT1-related conditions. |