Submissions for variant NM_000138.5(FBN1):c.4337-2A>G

dbSNP: rs794728216

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000181506	SCV000233809	pathogenic	not provided	2013-06-14	criteria provided, single submitter	clinical testing	c.4337-2 A>G: IVS35-2 A>G in intron 35 of the FBN1 gene (NM_000138.4)Although the c.4337-2 A>G mutation has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge, this mutation destroys the canonical splice acceptor site in intron 35 and is predicted to cause abnormal gene splicing. The mutation is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site mutations in the FBN1 gene have been reported in association with Marfan syndrome.In summary, c.4337-2 A>G in the FBN1 gene is interpreted as a disease-causing mutation. The variant is found in TAAD panel(s).
Ambry Genetics	RCV002314681	SCV000738858	pathogenic	Familial thoracic aortic aneurysm and aortic dissection	2016-12-14	criteria provided, single submitter	clinical testing	The c.4337-2A>G intronic pathogenic mutation results from an A to G substitution two nucleotides upstream from coding exon 35 in the FBN1 gene. This mutation has been previously reported in an individual meeting Ghent criteria for Marfan syndrome (Baudhuin LM et al. J. Hum. Genet. 2015;60(5):241-52). In addition to the clinical data presented in the literature, alterations that disrupt the canonical splice site are expected to cause aberrant splicing, resulting in an abnormal protein or a transcript that is subject to nonsense-mediated mRNA decay. As such, this alteration is classified as a disease-causing mutation.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659542	SCV000781369	likely pathogenic	Marfan syndrome	2016-11-01	criteria provided, single submitter	clinical testing