ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.5683T>C (p.Cys1895Arg) (rs878853686)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000227015 SCV000283639 likely pathogenic Marfan syndrome 2016-02-15 criteria provided, single submitter clinical testing This sequence change replaces cysteine with arginine at codon 1895 of the FBN1 protein (p.Cys1895Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in two individuals affected with Marfan syndrome. Currently there is insufficient evidence to conclude whether this variant segregates with disease or not (PMID: 11059536, 16222657). This variant is located in an EGF-like domain of the FBN1 protein and affects a cysteine (p.Cys1895) that is suggested to be involved in the formation of a disulfide bridge that is critical for protein folding (PMID: 3282918, 3495735, 4750422, 16677079). In addition, a different missense substitution at this codon (p.Cys1895Tyr) is reported to be deleterious (PMID: 19293843, 25304743). This indicates that the cysteine residue is important for FBN1 protein function. In summary, this variant is absent from population databases, has been observed in several patient with Marfan syndrome, and has a deleterious effect on protein function. For these reasons, this variant has been classified as Likely Pathogenic.
Ambry Genetics RCV000618650 SCV000738781 likely pathogenic Cardiovascular phenotype 2016-04-08 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Detected in individual satisfying established diagnostic critera for classic disease without a clear mutation,Rarity in general population databases (dbsnp, esp, 1000 genomes),In silico models in agreement (deleterious) and/or completely conserved position in appropriate species,Other strong data supporting pathogenic classification
Center for Medical Genetics Ghent,University of Ghent RCV000227015 SCV000787157 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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