ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.503G>T (p.Cys168Phe) (rs1555404803)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000521281 SCV000617200 pathogenic not provided 2017-10-17 criteria provided, single submitter clinical testing The C168F variant has not been published as pathogenic or been reported as benign to our knowledge, and it is not observed in large population cohorts (Lek et al., 2016). The C168F variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. The C168F variant affects a cysteine residue within an EGF-like domain of the FBN1 gene, which is predicted to affect disulfide bonding and alter the structure and function of the protein. Cysteine substitutions in the EGF-like domains represent the majority of pathogenic missense changes associated with FBN1-related disease (Collod-Béroud et al., 2003). Additionally, other missense variants at the same residue (C168R, C168G, C168W) have been reported in in HGMD in association with Marfan syndrome or ectopia lentis (Stenson et al., 2014).
Center for Human Genetics, Inc,Center for Human Genetics, Inc RCV000659503 SCV000781322 likely pathogenic Marfan syndrome 2016-11-01 criteria provided, single submitter clinical testing
Sangiuolo Lab - Medical Genetics Laboratory, Tor Vergata University RCV000659503 SCV000986960 likely pathogenic Marfan syndrome 2019-06-06 no assertion criteria provided clinical testing

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