ClinVar Miner

Submissions for variant NM_017646.6(TRIT1):c.968G>A (p.Arg323Gln)

gnomAD frequency: 0.00001  dbSNP: rs1047420796
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000623099 SCV000742560 pathogenic Inborn genetic diseases 2017-08-18 criteria provided, single submitter clinical testing
SIB Swiss Institute of Bioinformatics RCV000584728 SCV000883169 pathogenic Combined oxidative phosphorylation deficiency 35 2018-10-15 criteria provided, single submitter curation This variant is interpreted as Pathogenic, for Combined oxidative phosphorylation deficiency 35, autosomal recessive. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PP3 => Multiple lines of computational evidence support a deleterious effect on the gene or gene product. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/24901367). PS3-Very Strong => PS3 upgraded in strength to Very Strong (https://www.ncbi.nlm.nih.gov/pubmed/24901367).
Neuberg Centre For Genomic Medicine, NCGM RCV000584728 SCV005329536 likely pathogenic Combined oxidative phosphorylation deficiency 35 2023-05-20 criteria provided, single submitter clinical testing The observed missense variant c.968G>A(p.Arg323Gln) in TRIT1 gene has been reported previously in homozygous state inindividuals with Combined oxidative phosphorylation deficiency / mitochondrial disease (Whittaker RG, et al., 2015, Yarham JW, etal., 2014). The c.968G>A variant has 0.001% allele frequency in gnomAD Exomes. A different amino acid change p.Arg323Trp issubmitted to ClinVar as Pathogenic / Likely Pathogenic. This variant has been reported to the ClinVar database as Pathogenic.Theamino acid Arginine at position 323 is changed to a Glutamine changing protein sequence and it might alter its composition andphysico-chemical properties. Multiple lines of computational evidence (Polyphen, SIFT and Mutation Taster) predict a damaging effect on protein structure and function for this variant. The amino acid change p.Arg323Gln in TRIT1 is predicted as conserved byGERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Likely Pathogenic.
GeneDx RCV004797839 SCV005419443 pathogenic not provided 2024-05-31 criteria provided, single submitter clinical testing Reported in an adult with mitochondrial disease and epilepsy (PMID: 26381753); Expression studies in E. coli and yeast found that this variant impaired the isopentenyltransferase activity of TRIT1 (PMID: 24901367); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 26857223, 28185376, 24901367, 37393059, 26381753)
OMIM RCV000584728 SCV000692458 pathogenic Combined oxidative phosphorylation deficiency 35 2018-02-19 no assertion criteria provided literature only

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.