ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.968G>A (p.Arg323Gln)

gnomAD frequency: 0.00003  dbSNP: rs121918717
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 6
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000520296 SCV000617732 pathogenic not provided 2021-10-07 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect: marked reduction in enzyme activity (Candi et al., 1998; Herman et al., 2009); This variant is associated with the following publications: (PMID: 7824952, 9545389, 19241467, 31168818, 32105361, 31046801, 9593710, 23278109)
Invitae RCV000520296 SCV000955335 pathogenic not provided 2021-12-10 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 323 of the TGM1 protein (p.Arg323Gln). This variant is present in population databases (rs121918717, gnomAD 0.007%). This missense change has been observed in individuals with autosomal recessive congenital ichthyosis (PMID: 7824952, 9545389, 19241467, 23278109). It has also been observed to segregate with disease in related individuals. This variant is also known as 322Q. ClinVar contains an entry for this variant (Variation ID: 12484). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TGM1 protein function. Experimental studies have shown that this missense change affects TGM1 function (PMID: 9261103, 9593710). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000013303 SCV001554489 pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
OMIM RCV000013303 SCV000033550 pathogenic Autosomal recessive congenital ichthyosis 1 1995-01-27 no assertion criteria provided literature only
Counsyl RCV000013303 SCV000793786 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-08-30 no assertion criteria provided clinical testing
Natera, Inc. RCV000013303 SCV001459980 pathogenic Autosomal recessive congenital ichthyosis 1 2020-09-16 no assertion criteria provided 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.