Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001381631 | SCV001580113 | pathogenic | Multiple congenital exostosis | 2017-07-24 | criteria provided, single submitter | clinical testing | This sequence change results in a premature translational stop signal in the EXT1 gene (p.Leu667Ilefs*13). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 80 amino acids of the EXT1 protein. This variant is not present in population databases (ExAC no frequency). For these reasons, this variant has been classified as Pathogenic. Different truncations downstream of this variant (p.Gln685*, p.Tyr678*) have been determined to be pathogenic (PMID: 9521425, 25520924, 19810120). This suggests that deletion of this region of the EXT1 protein is causative of disease. This variant has not been reported in the literature in individuals with EXT1-related disease. |