ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.2627G>A (p.Cys876Tyr) (rs794728193)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181463 SCV000233765 likely pathogenic not provided 2017-05-24 criteria provided, single submitter clinical testing p.Cys876Tyr (TGC>TAC): c.2627 G>A in exon 22 of the FBN1 gene (NM_000138.4)The Cys876Tyr variant in the FBN1 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. The Cys876Tyr variant is a non-conservative amino acid substitution as these residues differ in polarity, charge, size and/or other properties and is more likely to impact secondary structure. The Cys876 residue is conserved across species. In silico analysis predicts Cys876Tyr is damaging to the protein structure/function. Mutations in nearby residues (Cys875Arg, Gly880Ser, Ala882Val) have been reported in association with Marfan syndrome, further supporting the functional importance of this region of the protein. Furthermore, the Cys876Tyr variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, while Cys876Tyr is a good candidate for a disease-causing mutation, with the clinical and molecular information available at this time we cannot unequivocally determine the clinical significance of this variant. The variant is found in TAAD panel(s).
Center for Medical Genetics Ghent,University of Ghent RCV000663560 SCV000786871 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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