ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.299G>A (p.Cys100Tyr) (rs397515782)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000220364 SCV000271224 likely pathogenic Marfan syndrome 2015-02-04 criteria provided, single submitter clinical testing The p.Cys100Tyr variant in FBN1 has been identified in 1 African American indivi dual with Marfan syndrome, 1 Chinese individual with Marfan syndrome, and segreg ated with disease in 1 affected relative (LMM unpublished data, Chung 2009). It was absent from large population studies. Additionally, another variant at the s ame position (p.Cys100Phe) has been identified to occur de novo in 1 Asian indiv idual with Marfan syndrome (LMM unpublished data), suggesting that a change at t his position may not be tolerated. Computational prediction tools and conservati on analysis suggest that the p.Cys100Tyr variant may impact the protein, though this information is not predictive enough to determine pathogenicity. Furthermor e, this variant affects a highly conserved cysteine residue in the EGF-like doma ins, which is a common finding in individuals with Marfan syndrome (Schrijver 19 99). In summary, although additional studies are required to fully establish its clinical significance, the p.Cys100Tyr variant is likely pathogenic.

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