ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.5825G>A (p.Cys1942Tyr)

dbSNP: rs794728241
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000687608 SCV000815185 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2018-04-08 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1942 of the FBN1 protein (p.Cys1942Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. 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 affects a cysteine residue located within an epidermal-growth-factor (EGF)–like 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: 10486319, 3495735, 4750422, 16677079). In addition, missense substitutions within the FBN1 EGF-like domains affecting cysteine residues are significantly overrepresented among individuals with Marfan syndrome (PMID: 16571647, 17701892). This variant has not been reported in the literature in individuals with FBN1-related disease. This variant is not present in population databases (ExAC no frequency).

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