ClinVar Miner

Submissions for variant NM_000138.4(FBN1):c.8087del (p.Asn2696fs) (rs1060501065)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464500 SCV000544905 likely pathogenic Marfan syndrome 2016-09-23 criteria provided, single submitter clinical testing This sequence change deletes 1 nucleotide from exon 65 of the FBN1 mRNA (c.8087delA), causing a frameshift at codon 2696. This creates a premature translational stop signal in the last exon of the FBN1 mRNA (p.Asn2696Thrfs*56). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 119 amino acids of the FBN1 protein. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN1-related disease. A different truncating variant downstream from this event (c.8534dup, p.Glu2846Argfs*5) has been determined to be pathogenic (PMID: 19293843). This suggests that the residues downstream are critical for FBN1 protein function and that other truncating variants that do not result in nonsense mediated decay may also be pathogenic. In summary, this variant is a novel deletion that affects residues critical for FBN1 function. This evidence indicates that the variant is pathogenic, but additional data is 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.