Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV001796796 | SCV002037603 | uncertain significance | Mitochondrial disease | 2021-12-10 | reviewed by expert panel | curation | The m.10455A>G variant in MT-TR was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). This variant has been reported only once in the literature (PMID: 23463613; Supp Table S1B) in the homoplasmic state in an individual from H haplogroup and mother was not available for testing. This does not meet criteria for PS4_supporting which requires at least two unrelated affected individuals. There are no large families reported in the medical literature to consider for evidence of segregation. There are several occurrences of this variant in GenBank sequences queried through MITOMAP on 6/29/2020 (seen in 1-4 individuals from several haplogroups including J1c, H1b, H1j, U5a, N1a for a total of 12/51,192 frequency). The computational predictor MitoTIP suggests this variant is likely benign (10th percentile) and HmtVAR predicts it to be likely polymorphic (BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP4. |
Wong Mito Lab, |
RCV000851003 | SCV000993237 | benign | Juvenile myopathy, encephalopathy, lactic acidosis AND stroke | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.10455A>G variant in MT-TR gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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, BS2, BP4 |