Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001879773 | SCV002246212 | likely pathogenic | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | 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. This variant is present in population databases (rs764622793, gnomAD 0.01%). 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). ClinVar contains an entry for this variant (Variation ID: 973463). 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. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
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 | |
| Fulgent Genetics, |
RCV005029841 | SCV005663872 | likely pathogenic | Aminoglycoside-induced deafness; Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2024-05-25 | criteria provided, single submitter | clinical testing | |
| Elsea Laboratory, |
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 |