ClinVar Miner

Submissions for variant NM_001365276.2(TNXB):c.12180C>G (p.Cys4060Trp)

gnomAD frequency: 0.00010  dbSNP: rs56345590
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Pediatric Services, National Institutes of Health, Clinical Center RCV000186504 SCV000222739 uncertain significance Ehlers-Danlos syndrome due to tenascin-X deficiency 2015-01-01 criteria provided, single submitter research
GeneDx RCV001731502 SCV001983207 uncertain significance not provided 2021-04-16 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Identified previously in conjunction with a fusion event involving TNXB and TNXA in individuals with a phenotype of congenital adrenal hyperplasia and hypermobile Ehlers-Danlos syndrome (Morissette et al., 2015; Demirdas et al., 2017); This variant is associated with the following publications: (PMID: 26075496, 31141158, 32572181, 31229653, 27582382)
PreventionGenetics, part of Exact Sciences RCV003907533 SCV004723342 uncertain significance TNXB-related disorder 2023-11-27 criteria provided, single submitter clinical testing The TNXB c.12174C>G variant is predicted to result in the amino acid substitution p.Cys4058Trp. Likely originated from the pseudogene TNXA, this variant can be presented in TNXB by itself in exon 40 or with the pseudogene-derived 120bp deletion across exon 35 and intron 35 due to a gene rearrangement event (unequal crossover or gene conversion). Located closer to the CYP21A2 gene (which is 3’ to 3’ with TNXB) in the RCCX locus, this variant alone (i.e. not with the 120bp deletion) can represent a different chimera TNXA/TNXB gene (Morissette et al. 2015. PubMed ID: 26075496; Chen et al. 2016. PubMed ID: 27297501; Miller and Merke. 2018. PubMed ID: 29734195). These studies suggested that this variant itself could be pathogenic. At this time, however, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. This variant is reported in 0.0055% of alleles in individuals of European descent in the large population variant database gnomAD (https://gnomad.broadinstitute.org/variant/6-32010262-G-C). This variant falls within a highly paralogous region. Allele frequency data should be interpreted with caution.

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.