ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.7726C>T (p.Arg2576Cys) (rs147195031)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000539171 SCV000627996 pathogenic Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2018-08-22 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 2576 of the FBN1 protein (p.Arg2576Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs147195031, ExAC 0.002%). This variant has been reported in individuals affected with Marfan's syndrome, including in the homozygous state in an affected individual from a consanguineous family (PMID: 23278365, 26272055, 26787436, 26787436) and has been reported in individuals in the Universal Mutation Database (PMID: 12938084). ClinVar contains an entry for this variant (Variation ID: 36118). This variant generates a cysteine residue in 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: 4750422, 16677079). Cysteine creating variants in these domains have been shown to affect protein stability and are overrepresented among individuals with Marfan syndrome (PMID: 15161917, 16571647, 17701892). For these reasons, this variant has been classified as Pathogenic.
Blueprint Genetics RCV000788741 SCV000927966 pathogenic not provided 2018-09-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000029780 SCV000052434 likely pathogenic Marfan syndrome 2015-10-02 no assertion criteria provided clinical testing
OMIM RCV000083258 SCV000115337 pathogenic Marfan syndrome, autosomal recessive 2013-10-01 no assertion criteria provided literature only
Center for Medical Genetics Ghent,University of Ghent RCV000029780 SCV000787353 uncertain significance Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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