Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV003069326 | SCV003466893 | uncertain significance | Exostoses, multiple, type 2 | 2023-09-25 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 488 of the EXT2 protein (p.Val488Ile). This variant is present in population databases (rs139153420, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with EXT2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2154521). 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. |
| Ambry Genetics | RCV003294465 | SCV003992945 | uncertain significance | Inborn genetic diseases | 2023-06-01 | criteria provided, single submitter | clinical testing | The c.1462G>A (p.V488I) alteration is located in exon 9 (coding exon 8) of the EXT2 gene. This alteration results from a G to A substitution at nucleotide position 1462, causing the valine (V) at amino acid position 488 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Baylor Genetics | RCV003069326 | SCV004192808 | uncertain significance | Exostoses, multiple, type 2 | 2023-08-28 | criteria provided, single submitter | clinical testing |