Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001219274 | SCV001391203 | uncertain significance | Osteogenesis imperfecta type I | 2019-04-23 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with COL1A1-related conditions. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant disrupts the c.543+5G nucleotide in the COL1A1 gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 25963598, Invitae). This suggests that this nucleotide is clinically-significant, and that variants that disrupt this position are likely to be disease-causing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This sequence change falls in intron 6 of the COL1A1 gene. It does not directly change the encoded amino acid sequence of the COL1A1 protein, but it affects a nucleotide within the consensus splice site of the intron. |