ClinVar Miner

Submissions for variant NM_000359.3(TGM1):c.430G>A (p.Gly144Arg)

gnomAD frequency: 0.00001  dbSNP: rs778635368
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000672768 SCV000797906 uncertain significance Autosomal recessive congenital ichthyosis 1 2018-02-14 criteria provided, single submitter clinical testing
Institute for Human Genetics and Genomic Medicine, Uniklinik RWTH Aachen RCV000672768 SCV002549099 likely pathogenic Autosomal recessive congenital ichthyosis 1 2022-06-23 criteria provided, single submitter clinical testing The detected change is reported in the dbSNP database (dbSNP151 as of 06/23/2022) with the designation rs778635368. In gnomAD it is listed with a frequency of 0.001061% (3/282772) (as of 06/23/2022). This variant has already been described several times in the literature in patients with ichthyosis (Hennies et al., 1998, Yamamoto et al., 2012). It is located in a mutation hotspot and is bioinformatically classified as "probably disease-causing" (PolyPhen2, Mutation Taster, SIFT, CADDphred 29.3). Based on the current state of knowledge, the variant can be classified as a "likely pathogenic variant" (ACMG criteria).
Baylor Genetics RCV000672768 SCV004203774 pathogenic Autosomal recessive congenital ichthyosis 1 2023-08-13 criteria provided, single submitter clinical testing
Invitae RCV003558520 SCV004296328 pathogenic not provided 2023-08-16 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with lamellar ichthyosis (PMID: 9545389, 11064247, 21895619). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs778635368, gnomAD 0.005%). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 144 of the TGM1 protein (p.Gly144Arg). ClinVar contains an entry for this variant (Variation ID: 556724). For these reasons, this variant has been classified as Pathogenic. 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.

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.