ClinVar Miner

Submissions for variant NM_000138.5(FBN1):c.1211C>T (p.Pro404Leu)

dbSNP: rs779930519
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
Labcorp Genetics (formerly Invitae), Labcorp RCV000814307 SCV000954710 likely benign Marfan syndrome; Familial thoracic aortic aneurysm and aortic dissection 2022-11-15 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001191447 SCV001359268 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-12-04 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 404 of the FBN1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/250990 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001191447 SCV002652607 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-05-25 criteria provided, single submitter clinical testing The p.P404L variant (also known as c.1211C>T), located in coding exon 10 of the FBN1 gene, results from a C to T substitution at nucleotide position 1211. The proline at codon 404 is replaced by leucine, an amino acid with similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
All of Us Research Program, National Institutes of Health RCV004803258 SCV005424924 uncertain significance Marfan syndrome 2024-07-20 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 404 of the FBN1 protein. Computational prediction tools and conservation analyses are inconclusive regarding the impact of this variant on the protein function. Computational splicing tools suggest that this variant may not impact RNA splicing. To our knowledge, functional assays have not been performed for this variant nor has this variant been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 1/250990 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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.