ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.3284G>A (p.Cys1095Tyr)

dbSNP: rs1597563934
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220691 SCV001392697 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2019-05-15 criteria provided, single submitter clinical testing This sequence change replaces cysteine with tyrosine at codon 1095 of the FBN1 protein (p.Cys1095Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant affects a cysteine residue in the EGF-like, TGFBP or hybrid motif domains of FBN1. Cysteine residues are believed to be involved in intramolecular disulfide bridges and have been shown to be important for FBN1 protein structure (PMID: 16905551, 19349279). In addition, missense substitutions affecting cysteine residues within these domains are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). This variant has not been reported in the literature in individuals with FBN1-related conditions. This variant is not present in population databases (ExAC no frequency).

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