ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.1453C>T (p.Arg485Cys) (rs137854485)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150705 SCV000198107 uncertain significance not specified 2018-02-15 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
Invitae RCV000809693 SCV000949859 uncertain significance Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces arginine with cysteine at codon 485 of the FBN1 protein (p.Arg485Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with Marfan syndrome or thoracic aortic aneurysms and dissections (PMID: 19839986, 16342915, 17568394, 24793577). ClinVar contains an entry for this variant (Variation ID: 16466). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
OMIM RCV000017930 SCV000038209 pathogenic Marfan syndrome, autosomal recessive 2007-09-01 no assertion criteria provided literature only
Center for Medical Genetics Ghent,University of Ghent RCV000663457 SCV000786750 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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