Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, |
RCV000623517 | SCV000740513 | pathogenic | not provided | 2017-07-03 | criteria provided, single submitter | clinical testing | |
Center for Human Genetics, |
RCV000659555 | SCV000781387 | likely pathogenic | Marfan syndrome | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Blueprint Genetics | RCV000623517 | SCV000927144 | likely pathogenic | not provided | 2017-02-09 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002343175 | SCV002651536 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2022-11-17 | criteria provided, single submitter | clinical testing | The p.C1876R variant (also known as c.5626T>C) is located in coding exon 45 of the FBN1 gene. This alteration results from a T to C substitution at nucleotide position 5626. The cysteine at codon 1876 is replaced by arginine, an amino acid with highly dissimilar properties. This alteration is located in the cbEGF-like #27 domain. A different alteration in the same codon, p.C1876Y, has been reported in a 27-year-old patient with aortic root dilation, dural ectasia, and ocular findings with a positive family history which was presumed to be pathogenic due to the high conservation of the cysteine residue in this cbEGF-like domain (Arbustini E et al. Hum Mutat. 2005;26(5):494). Based on internal structural assessment, this alteration eliminates a structurally critical disulfide bond in the structurally sensitive EGF/cbEGF domain #27. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the majority of available evidence to date, this variant is likely to be pathogenic. |