Submissions for variant NM_000138.5(FBN1):c.503G>T (p.Cys168Phe)

dbSNP: rs1555404803

Total submissions: 3

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