Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001955265 | SCV002208184 | uncertain significance | Multiple congenital exostosis | 2022-01-24 | 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 not expected to disrupt EXT1 protein function. This variant has not been reported in the literature in individuals affected with EXT1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.02%). This sequence change replaces phenylalanine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 250 of the EXT1 protein (p.Phe250Ile). |
| St. |
RCV002291791 | SCV002584582 | uncertain significance | Exostoses, multiple, type 1 | 2022-07-05 | criteria provided, single submitter | clinical testing | The EXT1 c.748T>A (p.Phe250Ile) missense change has a maximum subpopulation frequency of 0.023% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. 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. |