ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6425G>A (p.Cys2142Tyr) (rs794728335)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000181699 SCV000234002 pathogenic not provided 2014-10-03 criteria provided, single submitter clinical testing p.Cys2142Tyr (TGC>TAC): c.6425 G>A in exon 53 of the FBN1 gene (NM_000138.4) The C2142Y mutation in the FBN1 gene has been reported in an individual with classic Marfan syndrome (El-Aleem et al., 1999). C2142Y results in a non-conservative amino acid substitution resulting in a loss of a Cysteine residue, which may impact disulfide bonding. This substitution occurs at a position in the calcium binding EGF-like domain that is highly conserved across species. Mutations in nearby residues (G2140R, G2140E, I2143N, N2144D, N2144S) have been reported in association with Marfan syndrome, further supporting the functional importance of this region of the protein. Furthermore, the C2142Y mutation was not observed in approximately 6,500 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, C2142Y in the FBN1 gene is interpreted as a disease-causing mutation. The variant is found in TAAD panel(s).
Center for Medical Genetics Ghent,University of Ghent RCV000663870 SCV000787230 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

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