Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000631924 | SCV000753027 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2022-09-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant affects a cysteine residue in the EGF-like, TGFBP or hybrid motif domains of FBN1. Cysteine residues are believed to be involved in intramolecular disulfide bridges and have been shown to be important for FBN1 protein structure (PMID: 16905551, 19349279). In addition, missense substitutions affecting cysteine residues within these domains are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). 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: 527154). This missense change has been observed in individual(s) with FBN1-related conditions (Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 2204 of the FBN1 protein (p.Cys2204Arg). |
| Mendelics | RCV000678261 | SCV001139591 | likely pathogenic | Marfan syndrome | 2019-05-28 | criteria provided, single submitter | clinical testing | |
| Department of Medical Genetics, |
RCV000678261 | SCV000804302 | pathogenic | Marfan syndrome | 2018-06-01 | no assertion criteria provided | clinical testing |