ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.1904A>G (p.Tyr635Cys) (rs1555399816)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000623741 SCV000740502 likely pathogenic Marfan syndrome 2017-06-12 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc RCV000623741 SCV000781336 pathogenic Marfan syndrome 2016-11-01 criteria provided, single submitter clinical testing
Invitae RCV000684933 SCV000812396 pathogenic Marfan syndrome; Thoracic aortic aneurysm and aortic dissection 2018-08-11 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 635 of the FBN1 protein (p.Tyr635Cys). The tyrosine residue is moderately conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual affected with ectopia lentis (Invitae) and has been reported in other individuals with this condition or Marfan syndrome (PMID: 16222657, 18435798). ClinVar contains an entry for this variant (Variation ID: 520493). 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. For these reasons, this variant has been classified as Pathogenic.
Center for Medical Genetics Ghent,University of Ghent RCV000623741 SCV000786809 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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