ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.2942G>C (p.Cys981Ser)

dbSNP: rs727505110
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000156563 SCV000206282 likely pathogenic Marfan syndrome 2014-09-09 criteria provided, single submitter clinical testing The Cys981Ser variant in FBN1 has been reported in two individuals with clinical features of Marfan syndrome, 1 in which occured de novo (Sakai 2006; LMM unpubl ished data). It was absent from large population studies. Computational predicti on tools and conservation analysis suggest that this variant may impact the prot ein, though this information is not predictive enough to determine pathogenicity . In summary, although additional studies are required to fully establish its cl inical significance, the Cys981Ser variant is likely pathogenic.
GeneDx RCV004819995 SCV005441492 likely pathogenic not provided 2024-06-27 criteria provided, single submitter clinical testing Affects a cysteine residue within a TGF-binding protein domain (aka TB domain or 8-Cysteine domain) and is expected to disrupt disulfide bonding within this domain; other missense substitutions that affect cysteine residues within TGF-binding protein domains have been reported in association with FBN1-related disorders (PMIDs: 8281141, 21175431, 7622614; HGMD); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 8281141, 21175431, 7622614, 16835936, 19161152, 17627385)

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