Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001263554 | SCV004378501 | likely pathogenic | Exostoses, multiple, type 2 | 2023-12-27 | criteria provided, single submitter | clinical testing | This sequence change replaces asparagine, which is neutral and polar, with serine, which is neutral and polar, at codon 288 of the EXT2 protein (p.Asn288Ser). This variant is present in population databases (rs745738318, gnomAD 0.006%). This missense change has been observed in individual(s) with hereditary multiple osteochondromas (PMID: 30806661). ClinVar contains an entry for this variant (Variation ID: 983551). 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 with a negative predictive value of 80%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV001263554 | SCV001441615 | pathogenic | Exostoses, multiple, type 2 | 2020-11-06 | no assertion criteria provided | literature only |