Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002241442 | SCV001402506 | pathogenic | Ehlers-Danlos syndrome, classic type, 1 | 2024-01-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gly1351Argfs*14) in the COL5A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL5A1 are known to be pathogenic (PMID: 23587214). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with Ehlers-Danlos syndrome (PMID: 22696272). ClinVar contains an entry for this variant (Variation ID: 957118). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV002322109 | SCV002632404 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2018-01-29 | criteria provided, single submitter | clinical testing | The c.4050dupC pathogenic mutation, located in coding exon 51 of the COL5A1 gene, results from a duplication of C at nucleotide position 4050, causing a translational frameshift with a predicted alternate stop codon (p.G1351Rfs*14). This alteration has been reported in an individual with classic Ehlers-Danlos syndrome (Symoens S et al. Hum. Mutat., 2012 Oct;33:1485-93). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Human Genetics Bochum, |
RCV002241442 | SCV002758615 | likely pathogenic | Ehlers-Danlos syndrome, classic type, 1 | 2021-12-23 | criteria provided, single submitter | clinical testing | ACMG criteria used to clasify this variant: PVS1, PM2 |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003398984 | SCV004121832 | pathogenic | Ehlers-Danlos syndrome | 2023-10-19 | criteria provided, single submitter | clinical testing | Variant summary: COL5A1 c.4050dupC (p.Gly1351ArgfsX14) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 2.4e-05 in 248054 control chromosomes. c.4050dupC has been reported in the literature in individuals affected with Ehlers-Danlos Syndrome (example, Symoens_2012, Junkiert-Czarnecka_2022). The following publications have been ascertained in the context of this evaluation (PMID: 35723357, 22696272). Three submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |