Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001048523 | SCV001212534 | pathogenic | Multiple congenital exostosis | 2019-05-10 | criteria provided, single submitter | clinical testing | Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in EXT1 are known to be pathogenic (PMID: 10679937, 11391482, 19810120). For these reasons, this variant has been classified as Pathogenic. Disruption of this splice site has been observed in individuals affected with multiple osteochondromas (PMID: 19810120, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 5 of the EXT1 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
Gene |
RCV002509597 | SCV002818873 | pathogenic | not provided | 2023-01-04 | criteria provided, single submitter | clinical testing | Reported in a patient with multiple osteochondromas in published literature (Jennes et al., 2009); Canonical splice site variant predicted to result in a null allele in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 19810120) |