Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002010617 | SCV002290506 | uncertain significance | Multiple congenital exostosis | 2020-12-31 | 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. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces tyrosine with aspartic acid at codon 7 of the EXT1 protein (p.Tyr7Asp). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and aspartic acid. |