ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.4816+1G>T

dbSNP: rs1555397014
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV002314299 SCV000738764 pathogenic Familial thoracic aortic aneurysm and aortic dissection 2016-01-27 criteria provided, single submitter clinical testing The c.4816+1G>T intronic pathogenic mutation results from a G to T substitution one nucleotide downstream of coding exon 38 of the FBN1 gene. This alteration was reported in a cohort of patients with Marfan syndrome who met Ghent criteria (Baetens M et al, Hum. Mutat. 2011 Sep; 32(9):1053-62). In addition to the clinical data presented in the literature, since alterations that disrupt the canonical splice donor site are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Centre of Medical Genetics, University of Antwerp RCV000663750 SCV002025334 likely pathogenic Marfan syndrome 2021-03-01 criteria provided, single submitter research PM2, PS7, PP4
Labcorp Genetics (formerly Invitae), Labcorp RCV002531817 SCV003442878 pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-01-04 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 39 of the FBN1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in FBN1 are known to be pathogenic (PMID: 17657824, 19293843). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 519695). Disruption of this splice site has been observed in individuals with FBN1-related conditions (PMID: 21542060, 31471346).
Center for Medical Genetics Ghent, University of Ghent RCV000663750 SCV000787094 likely pathogenic Marfan syndrome 2017-11-07 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.