ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.2217T>G (p.Cys739Trp)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Petrovsky Russian Research Center of Surgery, The Federal Agency for Scientific Organizations RCV000791244 SCV000930149 pathogenic Marfan syndrome 2019-08-29 criteria provided, single submitter clinical testing The p.C739W is a novel variant found in one individual with MFS and is absent from large population studies (ExAC no frequency). There are two known missense variants at 739 codon (C739R, C739F) that were found in patients with MFS (PMID: 19293843; UMD-FBN1 ID: 2376). Cysteine residue located in cbEGF-like domain and participates in Disulfide bonds 727-739. Cysteine substitutions in EGF domains are common pathogenic mechanisms of the disease (PMID: 1301946, 15161917). Computational tools like Provean, SIFT, PolyPhen2 show deleterious effect. Additionally, near codons (C734, G737, Y746) are known mutation spots associated with MFS (PMID: 7611299, 12203987, 20564469). This suggests high importance of this region. Based on new evidences we evaluate C739W variant as Pathogenic.

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