ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6509G>A (p.Cys2170Tyr) (rs363821)

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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 RCV000150698 SCV000198069 likely pathogenic Marfan syndrome 2018-03-15 criteria provided, single submitter clinical testing The p.Cys2170Tyr variant in FBN1 has been identified as a de novo occurrence in 1 individual with a clinical diagnosis of Marfan syndrome (LMM data) and was abs ent from large population studies. This variant affects a cysteine residue; cyst eine substitutions are a common finding in individuals with Marfan syndrome (Sch rijver, 1999). Two other variants involving this residue, p.Cys2170Phe and p.Cys 2170Ser, have been associated with Marfan syndrome (Ng 2002, Tjeldhorn 2006), su ggesting that changes at this position are not tolerated. Computational predict ion tools and conservation analysis suggest that the p.Cys2170Tyr variant may im pact the protein, though this information is not predictive enough to determine pathogenicity. In summary, although additional studies are required to fully est ablish its clinical significance, the p.Cys2170Tyr variant is likely pathogenic. ACMG/AMP Criteria applied: PM1; PM2; PM6; PP3; PP4.

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