ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.6209G>T (p.Cys2070Phe) (rs1060501044)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000474831 SCV000544869 likely pathogenic Marfan syndrome 2016-05-30 criteria provided, single submitter clinical testing This sequence change replaces cysteine with phenylalanine at codon 2070 of the FBN1 protein (p.Cys2070Phe). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and phenylalanine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN1-related disease. This variant affects a cysteine residue located within an epidermal-growth-factor (EGF)-like domain of the FBN1 protein. Cysteine residues in these domains have been shown to be involved in the formation of disulfide bridges, which are critical for FBN1 protein structure and stability (PMID: 3495735, 4750422, 16677079). In addition, missense substitutions within the FBN1 EGF-like domains affecting cysteine residues are significantly overrepresented among patients with Marfan syndrome (PMID: 16571647, 17701892). For these reasons, this variant has been classified as Likely Pathogenic.

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