ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs780990272
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000256089 SCV000321962 pathogenic not provided 2019-10-23 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31168818, 18948357, 27025581, 19863506, 20137757, 19241467)
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
Invitae RCV000256089 SCV001588233 pathogenic not provided 2023-10-11 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 291 of the TGM1 protein (p.Gly291Asp). This variant is present in population databases (rs780990272, gnomAD 0.003%). This missense change has been observed in individuals with autosomal recessive congenital ichthyosis (PMID: 19241467, 19863506, 27025581, 28403434). ClinVar contains an entry for this variant (Variation ID: 265269). 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. This variant disrupts the p.Gly291 amino acid residue in TGM1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19262603, 30600594). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab RCV000666325 SCV002763818 pathogenic Autosomal recessive congenital ichthyosis 1 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000666325 SCV002780422 pathogenic Autosomal recessive congenital ichthyosis 1 2022-04-25 criteria provided, single submitter clinical testing
Baylor Genetics RCV000666325 SCV004203734 pathogenic Autosomal recessive congenital ichthyosis 1 2023-10-18 criteria provided, single submitter clinical testing
Counsyl RCV000666325 SCV000790598 likely pathogenic Autosomal recessive congenital ichthyosis 1 2017-03-31 no assertion criteria provided clinical testing
Natera, Inc. RCV000666325 SCV002091225 pathogenic Autosomal recessive congenital ichthyosis 1 2021-06-04 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.