Submissions for variant NM_000138.5(FBN1):c.3656A>G (p.Tyr1219Cys)

dbSNP: rs1555398394

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Blueprint Genetics	RCV000788488	SCV000927627	likely pathogenic	not provided	2018-04-12	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000663660	SCV000967702	likely pathogenic	Marfan syndrome	2019-07-20	criteria provided, single submitter	clinical testing	The p.Tyr1219Cys variant in FBN1 has been reported in at least 2 individuals with clinical features of Marfan syndrome (Arbustini 2005), including a de novo occurrence in one individual, and has also been reported in ClinVar (Variation ID 549181). This variant was absent from large population studies. Computational prediction tools and conservation analysis suggest that the p.Tyr1219Cys variant may impact the protein. In summary, although additional studies are required to fully establish its clinical significance, the p.Tyr1219Cys variant meets criteria to be classified as likely pathogenic for autosomal dominant Marfan syndrome. ACMG/AMP Criteria applied: PM2, PM6, PP3, PS4_supporting.
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV000788488	SCV002010144	pathogenic	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Centre of Medical Genetics, University of Antwerp	RCV000663660	SCV002025285	likely pathogenic	Marfan syndrome	2021-03-01	criteria provided, single submitter	research	PM2, PS1, PP4
Center for Medical Genetics Ghent, University of Ghent	RCV000663660	SCV000786988	likely pathogenic	Marfan syndrome	2017-11-07	no assertion criteria provided	clinical testing
Clinical Laboratory Sciences Program (CLSP), King Saud bin Abdulaziz University for Health Sciences (KSAU-HS)	RCV000663660	SCV003927910	pathogenic	Marfan syndrome	2023-04-01	no assertion criteria provided	clinical testing