Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001867715 | SCV002127591 | uncertain significance | Exostoses, multiple, type 2 | 2023-06-08 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with EXT2-related conditions. This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 149 of the EXT2 protein (p.Arg149Trp). This variant is present in population databases (rs757297287, gnomAD 0.05%). ClinVar contains an entry for this variant (Variation ID: 1368875). 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 not expected to disrupt EXT2 protein function. 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. |
| St. |
RCV001867715 | SCV005689040 | uncertain significance | Exostoses, multiple, type 2 | 2025-02-05 | criteria provided, single submitter | clinical testing | The EXT2 c.544C>T (p.Arg182Trp) missense change has a maximum subpopulation frequency of 0.009% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with hereditary multiple exostoses. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |