ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.6379+2T>C

dbSNP: rs113453570
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422144 SCV000516661 pathogenic not provided 2015-04-20 criteria provided, single submitter clinical testing The c.6379+2 T>C variant has not been reported as a pathogenic variant or as a benignpolymorphism to our knowledge; however, another substitution for the same position(c.6496+2T>G/IVS52+2T>G) has been reported in a 40 year-old individual with classical Marfansyndrome (Loeys et al., 2001). This c.6379+2 T>C substitution destroys the canonical splice donor site inintron 52 and is predicted to cause abnormal gene splicing. The variant is predicted to lead to either anabnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product ifthe message is used for protein translation. Other splice site variants in the FBN1 gene have beenreported in HGMD in association with Marfan/TAAD-related disorders (Stenson P et al., 2014).In summary, c.6379+2 T>C in the FBN1 gene is interpreted as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV003766214 SCV004610274 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2023-10-23 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 52 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). Disruption of this splice site has been observed in individual(s) with FBN1-related conditions (PMID: 35058154). ClinVar contains an entry for this variant (Variation ID: 379519). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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.