Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001002497 | SCV001160454 | pathogenic | not specified | 2019-04-19 | criteria provided, single submitter | clinical testing | The COL1A1 c.2829+1G>A variant (rs72653156), is reported in the literature in at least one individual affected with Osteogenesis imperfecta type IV (Marini 2007). This variant is absent from general population databases (1000 Genomes Project, Exome Variant Server, and Genome Aggregation Database), indicating it is not a common polymorphism. This variant abolishes the canonical splice donor site of intron 39, which is likely to disrupt gene function. Based on available information, the c.2829+1G>A variant is considered to be pathogenic. |
Invitae | RCV001869431 | SCV002235760 | pathogenic | Osteogenesis imperfecta type I | 2024-01-28 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 39 of the COL1A1 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 COL1A1 are known to be pathogenic (PMID: 7942841, 9295084, 9443882). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with osteogenesis imperfecta (PMID: 30886339). ClinVar contains an entry for this variant (Variation ID: 811967). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |