ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.1727G>A (p.Cys576Tyr) (rs1555399974)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000820849 SCV000961581 pathogenic Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2018-10-03 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 576 of the FBN1 protein (p.Cys576Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with Marfan syndrome (PMID: 18435798, 23684891). ClinVar contains an entry for this variant (Variation ID: 549038). 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. This variant disrupts the p.Cys576 amino acid residue in FBN1. Other variant(s) that disrupt this residue have been observed in affected individuals (PMID: 25652356), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Center for Medical Genetics Ghent,University of Ghent RCV000663486 SCV000786785 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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