Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Clin |
RCV004691091 | SCV005187329 | benign | Mitochondrial disease | 2024-02-12 | reviewed by expert panel | curation | The m.4336T>C variant in MT-TQ was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on February 12, 2024. This variant has not been reported in the medical literature as causative in individuals or families with primary mitochondrial disease to our knowledge. However, this variant has been reported to be associated with Parkinson and Alzheimer diseases. There are many occurrences of this variant in healthy population databases, including in gnomAD v3.1.2 (737/56,424 or 1.306%), in the Helix dataset (3,949/195,983 or 2.015%), and in the GenBank dataset (535/61,134 or 0.875%), and this variant is seen across haplogroups including haplogroups H, U, A, B, J, HV, K, L3, M, Z, T, C, and V (BA1). Computational predictors are discordant as MitoTIP suggests this variant is benign (37.7 percentile) and HmtVAR predicts it to be pathogenic (0.4). In summary, as association studies linking this variant with Parkinson and Alzheimer diseases are outside the scope of this curation, this variant meets criteria to be classified as benign for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on February 12, 2024. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BA1. |
| Center for Pediatric Genomic Medicine, |
RCV000224964 | SCV000281559 | uncertain significance | not provided | 2015-05-26 | criteria provided, single submitter | clinical testing | Converted during submission to Uncertain significance. |
| Wong Mito Lab, |
RCV000850736 | SCV000992969 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.4336T>C variant in MT-TQ gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS4 |
| Athena Diagnostics | RCV001288305 | SCV001475309 | benign | not specified | 2020-08-17 | criteria provided, single submitter | clinical testing | |
| OMIM | RCV000010239 | SCV000030463 | pathogenic | Sensorineural deafness and migraine | 2001-06-01 | no assertion criteria provided | literature only |