Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002240562 | SCV001234414 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2021-08-27 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 16 of the COL5A1 gene. It does not directly change the encoded amino acid sequence of the COL5A1 protein. It affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs369608154, ExAC 0.002%). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. Variants that disrupt 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. 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. |
| Ambry Genetics | RCV002411606 | SCV002715579 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2020-12-18 | criteria provided, single submitter | clinical testing | The c.1828-3C>G intronic variant results from a C to G substitution 3 nucleotides upstream from coding exon 17 in the COL5A1 gene. This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |