Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001378485 | SCV001576061 | likely pathogenic | not provided | 2020-07-13 | criteria provided, single submitter | clinical testing | 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. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in TRMU are known to be pathogenic (PMID: 19732863, 23625533). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with TRMU-related conditions. This variant is present in population databases (rs768299416, ExAC 0.01%). This sequence change affects an acceptor splice site in intron 2 of the TRMU gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001826140 | SCV002571934 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2022-08-10 | criteria provided, single submitter | clinical testing | Variant summary: TRMU c.249-2A>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes the canonical 3' acceptor site. Two predict the variant creates a cryptic 5' donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 249714 control chromosomes (gnomAD). To our knowledge, no occurrence of c.249-2A>G in individuals affected with Liver Failure Acute Infantile, Transient and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV002499781 | SCV002813631 | likely pathogenic | Aminoglycoside-induced deafness; Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2022-03-15 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003473909 | SCV004204395 | likely pathogenic | Aminoglycoside-induced deafness | 2022-12-30 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV001826140 | SCV002076152 | likely pathogenic | Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins | 2021-05-28 | no assertion criteria provided | clinical testing |