Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002310868 | SCV000319317 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2014-08-08 | criteria provided, single submitter | clinical testing | The p.G880D variant (also known as c.2639G>A), located in coding exon 21 of the FBN1 gene, results from a G to A substitution at nucleotide position 2639. The glycine at codon 880 is replaced by aspartic acid, an amino acid with some similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6,493 samples (12,986 alleles) with coverage at this position. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Two other alterations of the same codon in the hybrid motif #02 domain, p.G880S (c.2638G>A) and p.G880R (c.2638G>C), have been reported. The recurrent p.G880S (c.2638G>A) mutation was detected in multiple patients with classic Marfan syndrome (Rommel K et al. Hum Mutat. 2002; 20(5):406-7; Attanasio M et al. Clin Genet. 2008; 74(1):39-46). Based on the majority of available evidence to date, the p.G880D variant is likely to be pathogenic. |
| Gene |
RCV000418771 | SCV000531385 | likely pathogenic | not provided | 2024-06-26 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); Does not affect a cysteine or calcium-binding residue within an EGF-like domain or a TGF-binding protein domain of the FBN1 gene; cysteine substitutions in the EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disorders (PMID: 12938084); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12938084, 32534992, 33824467, 34422331, 27724990) |
| Department of Vascular Biology, |
RCV001374788 | SCV001439553 | uncertain significance | Isolated thoracic aortic aneurysm | 2018-09-01 | flagged submission | research |