Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000812017 | SCV000952315 | pathogenic | Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection | 2019-10-23 | 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). This variant has been reported to affect FBN1 protein function (PMID: 27893734). This variant has been observed to be de novo in individuals affected with Marfan syndrome (PMID: 8136837, 10486319) and has been observed in additional individuals affected with Marfan syndrome (PMID: 9401003, 19002209, 27906200). This variant is also known as C344Y in the literature. ClinVar contains an entry for this variant (Variation ID: 16429). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with tyrosine at codon 1242 of the FBN1 protein (p.Cys1242Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. |
| Centre of Medical Genetics, |
RCV000017891 | SCV002025286 | pathogenic | Marfan syndrome | 2021-03-01 | criteria provided, single submitter | research | PM2, PVS2, PP4 |
| Institute of Medical Genetics and Genomics, |
RCV000017891 | SCV003935299 | pathogenic | Marfan syndrome | criteria provided, single submitter | clinical testing | The heterozygous variant c.3725G>A (p.Cys1242Tyr) has been identified in a proband with severe myopia, marfanoid habits, hindfoot deformity, long slender fingers, chest deformity, mitral valve prolapsed and increased arm span. This variant is present in a mutation hotspot region where 4 pathogenic variants (PM1_moderate) have been reported and 1444 missense pathogenic variants in FBN1 gene have been reported (PP2_supporting). This variant is not found in gnomAD (Aggregated) (PM2_Moderate). This has been previously reported PMID: 19002209 (PP5_very strong). | |
| OMIM | RCV000017891 | SCV000038170 | pathogenic | Marfan syndrome | 1994-01-01 | no assertion criteria provided | literature only | |
| Center for Medical Genetics Ghent, |
RCV000017891 | SCV000786991 | likely pathogenic | Marfan syndrome | 2017-11-07 | no assertion criteria provided | clinical testing |