Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002310907 | SCV000319455 | likely pathogenic | Familial thoracic aortic aneurysm and aortic dissection | 2022-07-07 | criteria provided, single submitter | clinical testing | The p.G2195R variant (also known as c.6583G>A), located in coding exon 53 of the FBN1 gene, results from a G to A substitution at nucleotide position 6583. The glycine at codon 2195 is replaced by arginine, an amino acid with dissimilar properties. This alteration has been reported in individuals with a clinical diagnosis of Marfan syndrome (Stheneur C et al. Eur J Hum Genet, 2009 Sep;17:1121-8), as well as in individuals with concerns for Marfan syndrome (Comeglio P et al. Hum Mutat, 2007 Sep;28:928; Ambry internal data). This variant is considered to be rare based on population 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. |
| Invitae | RCV000700740 | SCV000829509 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2021-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 2195 of the FBN1 protein (p.Gly2195Arg). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. ClinVar contains an entry for this variant (Variation ID: 263922). This missense change has been observed in individual(s) with clinical features of Marfan syndrome (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). |
| Centre of Medical Genetics, |
RCV000663880 | SCV002025401 | likely pathogenic | Marfan syndrome | 2021-03-01 | criteria provided, single submitter | research | PM2, PS1, PP4 |
| Center for Medical Genetics Ghent, |
RCV000663880 | SCV000787245 | uncertain significance | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |