ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.299G>T (p.Cys100Phe) (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 RCV000035157 SCV000058798 likely pathogenic Marfan syndrome 2012-04-19 criteria provided, single submitter clinical testing The Cys100Phe variant (FBN1) has not been reported in the literature nor previou sly identified by our laboratory. A different change at the same amino acid (Cys 100Tyr) has been reported in one individual with Marfan syndrome and was absent in 100 control chromosomes (Chung 2009), suggesting that changes to this positio n may not be tolerated. In addition, computational analyses (biochemical amino a cid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) suggest that the C ys100Phe variant may impact the protein. Furthermore, this variant affects a cys teine residue; cysteine substitutions are a common finding in individuals with M arfan syndrome (Schrijver 1999). In summary, this variant is likely to be pathog enic, though segregation studies and functional analyses are required to fully e stablish the pathogenicity of this variant. The clinical significance of this s equence variant should be interpreted in the context of this individual's clinic al manifestation.

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