Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000492855 | SCV000582182 | likely pathogenic | not provided | 2019-04-29 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Affects a cysteine residue within a TGF-binding protein domain (aka TB domain or 8-Cysteine domain) and is expected to disrupt disulfide bonding within this domain; other missense substitutions that affect cysteine residues within this TGF-binding protein domain have been reported in association with various FBN1-related phenotypes, including Marfan syndrome (Stenson et al., 2014).; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 9338581) |
| Labcorp Genetics |
RCV001064950 | SCV001229887 | likely pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2019-05-27 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Cys2111 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in individuals with FBN1-related conditions (PMID: 11826022), which suggests that this may be a clinically significant amino acid residue. 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). This variant has been observed in an individual affected with Marfan syndrome (PMID: 9338581). ClinVar contains an entry for this variant (Variation ID: 429578). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 2111 of the FBN1 protein (p.Cys2111Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Baylor Genetics | RCV001334258 | SCV001527052 | pathogenic | Marfan syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing |