Submissions for variant NM_000138.5(FBN1):c.5208T>A (p.Cys1736Ter)

dbSNP: rs794728234

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181539	SCV000233842	pathogenic	not provided	2014-03-30	criteria provided, single submitter	clinical testing	p.Cys1736Stop (TGT>TGA): c.5208 T>A in exon 42 of the FBN1 gene (NM_000138.4)To our knowledge, the C1736X mutation in the FBN1 gene has not been reported in a peer reviewed journal as a disease-causing mutation or as a benign polymorphism. C1736X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense mutations in the FBN1 gene have been reported in association with Marfan syndrome. In summary, C1736X in the FBN1 gene is interpreted as a disease-causing mutation.The variant is found in TAAD panel(s).
Ambry Genetics	RCV005338097	SCV006002747	pathogenic	Familial thoracic aortic aneurysm and aortic dissection	2025-01-17	criteria provided, single submitter	clinical testing	The p.C1736* pathogenic mutation (also known as c.5208T>A), located in coding exon 41 of the FBN1 gene, results from a T to A substitution at nucleotide position 5208. This changes the amino acid from a cysteine to a stop codon within coding exon 41. This variant has been reported in association with Marfan syndrome (Spits C et al. Fertil Steril, 2006 Aug;86:310-20). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.
Center for Medical Genetics Ghent, University of Ghent	RCV000663767	SCV000787116	pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing