ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.872G>A (p.Gly291Asp) (rs780990272)

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
GeneDx RCV000256089 SCV000321962 likely pathogenic not provided 2016-08-04 criteria provided, single submitter clinical testing The G291D missense variant in the TGM1 gene has been reported previously in patients with autosomal recessive congenital ichthyosis (Farasat et al., 2009; Herman et al., 2009). This variant was also observed in several patients referred for testing at GeneDx, including a patient who was homozygous for this variant. It 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. G291D 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Missense variants at the same codon (G291S) and in nearby residues (R286Q, N289T, F293V) have been reported in the Human Gene Mutation Database in association with ichththyosis (Stenson et al., 2014), supporting the functional importance of this region of the protein. We interpret G291D as a very strong candidate for a pathogenic variant.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000256089 SCV000609826 pathogenic not provided 2017-03-06 criteria provided, single submitter clinical testing
Counsyl RCV000666325 SCV000790598 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-03-31 criteria provided, single submitter 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.