ClinVar Miner

Submissions for variant NM_018006.5(TRMU):c.680G>C (p.Arg227Thr)

gnomAD frequency: 0.00002  dbSNP: rs764622793
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
Invitae RCV001879773 SCV002246212 likely pathogenic not provided 2023-09-08 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 227 of the TRMU protein (p.Arg227Thr). This variant is present in population databases (rs764622793, gnomAD 0.01%). This missense change has been observed in individual(s) with transient infantile liver failure (PMID: 28973083, 30740308, 33365252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 973463). 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 TRMU protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002298915 SCV002598916 uncertain significance not specified 2023-08-03 criteria provided, single submitter clinical testing Variant summary: TRMU c.680G>C (p.Arg227Thr) results in a non-conservative amino acid change in the encoded protein sequence. Three of three in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 251470 control chromosomes (gnomAD). c.680G>C has been reported in the literature as a biallelic genotype in individuals affected with Liver Failure Acute Infantile, Transient (example, Meng_2017 cited in Soler-Alfanso_2019, Sala-Coromina_2021). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 28973083, 33485800, 33365252, 30740308, 36305855). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as likely pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics RCV003473836 SCV004204370 pathogenic Aminoglycoside-induced deafness 2023-07-23 criteria provided, single submitter clinical testing
Elsea Laboratory, Baylor College of Medicine RCV001250083 SCV001424255 likely pathogenic Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins 2020-04-01 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.