ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.832G>A (p.Gly278Arg)

gnomAD frequency: 0.00002  dbSNP: rs121918725
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 10
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000439800 SCV000514898 pathogenic not provided 2022-11-21 criteria provided, single submitter clinical testing Biochemical assays of transglutaminase 1 with the amino acid substitution demonstrated markedly reduced activity of the epidermal transglutaminase 1 protein (Raghunath et al., 2003); This variant is associated with the following publications: (PMID: 12542526, 11298529, 22311480, 23689228, 30693114, 28403434)
Counsyl RCV000013315 SCV000791977 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-06-02 criteria provided, single submitter clinical testing
Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University RCV000013315 SCV000891558 pathogenic Autosomal recessive congenital ichthyosis 1 2024-06-12 criteria provided, single submitter curation
Invitae RCV000439800 SCV000933752 pathogenic not provided 2023-10-27 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 278 of the TGM1 protein (p.Gly278Arg). This variant is present in population databases (rs121918725, gnomAD 0.006%). This missense change has been observed in individuals with TGM1-related conditions (PMID: 22311480, 23689228, 28403434). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 12492). 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 with a positive predictive value of 95%. 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.
Genome-Nilou Lab RCV000013315 SCV002763840 likely pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Baylor Genetics RCV000013315 SCV004203784 pathogenic Autosomal recessive congenital ichthyosis 1 2024-03-26 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000013315 SCV005051981 pathogenic Autosomal recessive congenital ichthyosis 1 2024-02-01 criteria provided, single submitter curation
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004689415 SCV005184975 pathogenic Lamellar ichthyosis 2024-05-23 criteria provided, single submitter clinical testing Variant summary: TGM1 c.832G>A (p.Gly278Arg) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2.8e-05 in 251426 control chromosomes. c.832G>A has been reported in the literature in individuals affected with Congenital Ichthyosis in both the homozygous and compound heterozygous state (e.g. Marukian_2017, Raghunath_2003, Youssefian_2019). These data indicate that the variant is likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal transglutaminase 1 activity in vitro (Raghunath_2003). The following publications have been ascertained in the context of this evaluation (PMID: 28403434, 12542526, 30578701). ClinVar contains an entry for this variant (Variation ID: 12492). Based on the evidence outlined above, the variant was classified as pathogenic.
OMIM RCV000013315 SCV000033561 pathogenic Autosomal recessive congenital ichthyosis 1 2003-02-01 no assertion criteria provided literature only
Natera, Inc. RCV000013315 SCV001459985 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.