ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1982G>A (p.Cys661Tyr)

dbSNP: rs1060501086
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001381625 SCV001580103 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2016-07-18 criteria provided, single submitter clinical testing This variant has been reported in individuals affected with Marfan syndrome (PMID: 12203992, 26787436). This variant affects a cysteine residue located within an TGFBP domain of the FBN1 protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for FBN1 protein structure and stability (PMID: 11104663, 12203987, 16677079). In addition, missense substitutions within the TGFBP domains affecting cysteine residues are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). For these reasons, this variant has been classified as Pathogenic. This sequence change replaces cysteine with tyrosine at codon 661 of the FBN1 protein (p.Cys661Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency).
Centre of Medical Genetics, University of Antwerp RCV000467145 SCV002025525 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS5, PP4

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