ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.8012T>C (p.Leu2671Pro)

dbSNP: rs2141214610
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
Labcorp Genetics (formerly Invitae), Labcorp RCV001963568 SCV002251383 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2021-10-24 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt FBN1 protein function. This missense change has been observed in individuals with Marfan syndrome (PMID: 25652356; Invitae). This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 2671 of the FBN1 protein (p.Leu2671Pro).
Department of Laboratory Medicine and Genetics, Samsung Medical Center RCV005050489 SCV005684923 likely pathogenic Marfan syndrome 2025-01-02 no assertion criteria provided clinical testing The NM_000138.5:c.8012T>C is considered to be rare in the general population database (gnomAD v2.1.1). This variant is predicted to be deleterious by in-silico analysis (REVEL). This variant was found in a patient with Marfan syndrome meeting revised Ghent criteria (aortic root dilatation and a systemic score of 7 points) (Samsung Medical Center internal data). According to the ClinGen guidance for PP1/BS4 and PP4 criteria (PMID: 38103548), PP4 with weighted strength was applied. In summary, this variant was classified as a likely pathogenic variant for Marfan syndrome (PP2, PP3, PP4 with weighted strength, PM2_P).

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.