ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.529T>C (p.Cys177Arg) (rs363853)

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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 RCV000035222 SCV000058867 likely pathogenic Marfan syndrome 2012-10-04 criteria provided, single submitter clinical testing The p.Cys177Arg variant in FBN1 has been reported as a de novo change in 2 indiv iduals, a 4 year old individual with isolated ectopia lentis and an individual r eferred for aortopathy genetc testing (Arbustini 2005, Yang 2016). It was also i dentified in 1 individual with a clinical diagnosis of Marfan syndrome (LMM data ). In addition, two different amino acid changes have been reported at the same residue (p.Cys177Ser and p.Cys177Tyr) in two individuals with clinical features of Marfan syndrome (Attanasio 2008), suggesting that changes at this position ma y not be tolerated. This variant impacts a cysteine residue and cysteine substit utions in the calcium-binding EGF-like domains represent the majority of pathoge nic missense changes associated with Marfan syndrome. Computational prediction t ools and conservation analysis are consistent with pathogenicity. In summary, al though additional studies are required to fully establish its clinical significa nce, the p.Cys177Arg variant is likely pathogenic. ACMG/AMP Criteria applied: PM 1, PM2, PM6, PP3, PS4_Supporting.

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