ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.4757G>A (p.Arg1586Gln) (rs143195229)

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 RCV000196903 SCV000250216 uncertain significance not provided 2016-05-24 criteria provided, single submitter clinical testing The R1586Q variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R1586Q variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved in mammals. However, no missense mutations in nearby residues have been reported in the Human Gene Mutation Database. However, the R1586Q variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant.
Ambry Genetics RCV000249340 SCV000318329 uncertain significance Cardiovascular phenotype 2013-01-31 criteria provided, single submitter clinical testing Co-segregation data for this variant is currently unavailable. This variant has not been detected in conjunction with a pathogenic mutation to date. Allele frequency data in population-based cohorts is not currently available. This amino acid position is well conserved in available vertebrate species except for wallaby and opossum, and the flanking regions are also fairly conserved.This alteration is predicted to be benign with a score of 0.275 (sensitivity: 0.87; specificity: 0.74)This alteration is predicted to be tolerated with a score of 0.590 (conservation: 1.62)

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.