ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6049T>C (p.Cys2017Arg)

dbSNP: rs1555395486
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000548249 SCV000627953 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-05-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. A different missense substitution at this codon (p.Cys2017Trp) has been determined to be pathogenic (PMID: 25907466). This suggests that the cysteine residue is critical for FBN1 protein function and that other missense substitutions at this position may also be 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 patients with Marfan syndrome (PMID: 16571647, 17701892). This variant has been reported in an individual affected with Marfan syndrome (PMID: 10464652). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 2017 of the FBN1 protein (p.Cys2017Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769633 SCV000901033 likely pathogenic Familial thoracic aortic aneurysm and aortic dissection 2016-07-22 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002490964 SCV002793709 likely pathogenic Ectopia lentis 1, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2, dominant; Acromicric dysplasia; Geleophysic dysplasia 2; Progeroid and marfanoid aspect-lipodystrophy syndrome 2022-01-04 criteria provided, single submitter clinical testing

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