ClinVar Miner

Submissions for variant NM_001999.4(FBN2):c.76A>G (p.Thr26Ala) (rs374922166)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197630 SCV000250142 uncertain significance not specified 2015-09-28 criteria provided, single submitter clinical testing The T26A variant has not been published as a pathogenic variant or reported as a benign variant to our knowledge. However, it has been seen in multiple individuals who had DNA-based testing for Marfan syndrome/TAAD at GeneDx. The T26A variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. In addition, the T26A variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Nevertheless, this substitution occurs at a position that is not conserved across species, with A26 present in two mammalian species and two non-mammalian species. Furthermore, in silico analysis predicts this variant likely does not alter the protein structure/function. Moreover, the T26A variant does not affect a Cysteine residue within a calcium-binding EGF-like domain of the FBN2 gene. Cysteine substitutions in the calcium-binding EGF-like domains represent the majority of pathogenic missense changes associated with FBN2-related disorders (Collod-Beroud et al., 2003).
Ambry Genetics RCV000246511 SCV000318117 likely benign Cardiovascular phenotype 2019-05-03 criteria provided, single submitter clinical testing In silico models in agreement (benign);Subpopulation frequency in support of benign classification
Invitae RCV001083543 SCV000630258 benign Congenital contractural arachnodactyly 2020-07-22 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000726832 SCV000703466 uncertain significance not provided 2016-12-09 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001083543 SCV001316686 likely benign Congenital contractural arachnodactyly 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.

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.