Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001348233 | SCV001542527 | likely pathogenic | Multiple congenital exostosis | 2021-03-04 | criteria provided, single submitter | clinical testing | 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. 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 been observed in individual(s) with clinical features of hereditary multiple osteochondromas (Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 153 of the EXT1 protein (p.Leu153Pro). The leucine residue is moderately conserved and there is a moderate physicochemical difference between leucine and proline. |