ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.8447A>C (p.His2816Pro)

dbSNP: rs1555393532
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 RCV000803523 SCV000943401 likely pathogenic Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2018-10-31 criteria provided, single submitter clinical testing This sequence change replaces histidine with proline at codon 2816 of the FBN1 protein (p.His2816Pro). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and proline. 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has been observed to be de novo in an individual with clinical features of Marfan syndrome (Invitae). ClinVar contains an entry for this variant (Variation ID: 549464). This variant is not present in population databases (ExAC no frequency).
Center for Medical Genetics Ghent, University of Ghent RCV000664025 SCV000787417 uncertain significance 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.