Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000376607 | SCV000478525 | uncertain significance | Ehlers-Danlos syndrome type 7A | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001861347 | SCV002267173 | uncertain significance | Ehlers-Danlos syndrome, classic type, 1 | 2021-10-21 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 8 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. 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. 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. ClinVar contains an entry for this variant (Variation ID: 365711). This variant has not been reported in the literature in individuals affected with COL5A1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). |
Ambry Genetics | RCV002379259 | SCV002692927 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2018-05-17 | criteria provided, single submitter | clinical testing | The c.1332+4dupA intronic variant results from a duplication of one A nucleotide at 4 nucleotides after coding exon 8 of the COL5A1 gene. This nucleotide position is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |