Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000686140 | SCV000813644 | pathogenic | Multiple congenital exostosis | 2018-06-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). A different variant (c.538_539delAG) giving rise to the same protein effect observed here (p.Leu181Profs*7) has been reported in individuals affected with mutliple osterochondromas and multiple exostosis (PMID: 18165274, Invitae), indicating that this residue may be critical for protein function. This variant has not been reported in the literature in individuals with EXT1-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Leu181Profs*7) in the EXT1 gene. It is expected to result in an absent or disrupted protein product. |