Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Service de Biochimie Médicale et Biologie Moléculaire, |
RCV001248809 | SCV001338778 | pathogenic | Multiple congenital exostosis | 2020-06-17 | criteria provided, single submitter | clinical testing | Absent from ExAC and gnomAD. Variants affecting the same nucleotide reported as responsible for multiple exostosis disease in databases and in the literature (c.1633-1G> T in ClinVar; c.1633-1G> C in LOVD and by Jennes I. et al., Hum. Mutat. 2009). Variant affecting consensus acceptor splice site of exon 8. |
Invitae | RCV001248809 | SCV003325864 | pathogenic | Multiple congenital exostosis | 2022-03-11 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 972704). Disruption of this splice site has been observed in individual(s) with multiple exostoses (PMID: 16088908, 19810120). This variant is not present in population databases (gnomAD no frequency). This sequence change affects an acceptor splice site in intron 7 of the EXT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site 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). |