ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.4049G>T (p.Cys1350Phe) (rs1555397718)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000767967 SCV000898694 likely pathogenic Ectopia lentis, isolated, autosomal dominant; Marfan syndrome; MASS syndrome; Stiff skin syndrome; Weill-Marchesani syndrome 2; Acromicric dysplasia; Geleophysic dysplasia 2; Marfan lipodystrophy syndrome 2018-04-30 criteria provided, single submitter clinical testing FBN1 NM_000138.4 exon 33 p.Cys1350Phe (c.4049G>T): This variant has been reported in the literature in 1 individual with Marfan syndrome (Baetens 2011 PMID:21542060) and is not present in large control databases. Evolutionary conservation and computational predictive tools suggest that this variant may impact the protein. Of note, this variant is predicted to affect a cysteine residue. Cysteine in the FBN1 gene is reported to have important functional relevance; variants that involve a cysteine residue are reported to be particularly significant (Dietz 1992 PMID1301946). Furthermore, other variants at this same codon (p.Cys1350Arg, p.Cys1350Ser, p.Cys1350Tyr) have been reported in the literature, supporting that this region is significant. In summary, data on this variant is highly suspicious for disease, but requires further evidence for pathogenicity. Therefore, this variant classified as likely pathogenic.
Center for Medical Genetics Ghent,University of Ghent RCV000663688 SCV000787019 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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