Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002433597 | SCV002751627 | pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-03 | criteria provided, single submitter | clinical testing | The p.G924S pathogenic mutation (also known as c.2770G>A), located in coding exon 39 of the COL3A1 gene, results from a G to A substitution at nucleotide position 2770. The glycine at codon 924 is replaced by serine, an amino acid with similar properties. The majority (approximately two-thirds) of COL3A1 mutations identified to date have involved the substitution of another amino acid for glycine within the triple-helical domain (Pepin MG et al. Genet Med. 2014;16(12):881-8; Frank M et al. Eur J Hum Genet. 2015;23(12):1657-64). This particular glycine substitution has been reported in individuals with vascular Ehlers-Danlos syndrome (Ambry internal data; Pepin MG et al. Genet Med, 2014 Dec;16:881-8). Internal structural analysis indicates that this alteration disrupts the characteristic G-X-Y motif in the COL3A1 protein and inserts a bulky side chain into a sterically-constrained region (Bella J et al. Science. 1994;266:75-81; Hohenester E et al. Proc. Natl. Acad. Sci. U.S.A. 2008;105:18273-7; Ambry internal data). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. |
| Collagen Diagnostic Laboratory, |
RCV000087554 | SCV000120441 | pathogenic | Ehlers-Danlos syndrome, type 4 | no assertion criteria provided | clinical testing |