ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.4248+2T>C

dbSNP: rs112274185
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056827 SCV001221291 pathogenic Osteogenesis imperfecta type I 2019-06-20 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in the last intron (intron 50) of the COL1A1 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (ExAC no frequency). Disruption of this splice site has been observed in individuals affected with osteogenesis imperfecta type 3 or prenatal onset of multiple fractures (PMID: 25963598, Invitae), of whom it has been observed de novo in at least one individual (Invitae). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID:25963598). For these reasons, this variant has been classified as Pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.