Submissions for variant NM_000138.4(FBN1):c.7819+1G>A (rs112907302)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493377	SCV000582719	pathogenic	not provided	2015-09-27	criteria provided, single submitter	clinical testing	The c.7819+1G>A pathogenic variant in the FBN1 gene has been reported previously in a French family with classical Marfan syndrome and was not detected in 200 French control individuals. (Stheneur et al., 2009). This splice site variant destroys the canonical splice donor site in intron 63. It is predicted to cause abnormal gene splicing, either leading to 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. The c.7819+1G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Pathogenic variants involving the intron 63 splice donor site (c.7819+3A>C, c.7819+5G>A) have been previously reported in the Human Gene Mutation Database in association with Marfan syndrome (Stenson et al., 2014), supporting the importance of this region of the gene. We interpret c.7819+1G>A as a pathogenic variant.
Center for Medical Genetics Ghent,University of Ghent	RCV000663981	SCV000787363	likely pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing