Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003985434 | SCV004801739 | uncertain significance | Mitochondrial disease | 2023-08-22 | reviewed by expert panel | curation | The m.12217A>G variant in MT-TS2 was reviewed by the Mitochondrial Disease Variant Curation Expert Panel on August 22, 2023. This variant has not been reported in the medical literature as causative in affected individuals or families with primary mitochondrial disease to our knowledge. There are several occurrences in population databases. The frequency in the MITOMAP GenBank sequences is 12/61,168 (0.020%). The frequency in the Helix dataset is 186/195,983 (0.095%) homoplasmic occurrences in addition to six heteroplasmic occurrences. The frequency in gnomAD v3.1.2 is 35/56,434 (0.062%). In all three population databases, this variant is seen in individuals from different haplogroups. MitoTIP suggests this variant is benign (5.8th percentile; BP4). There are no cybrids, single fiber studies, or other functional assays 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. We note that three experts on this panel felt likely benign was a more appropriate classification given the frequency in the general population and poor conservation at this site however the majority (four) agreed with uncertain significance. This classification was approved by the NICHD/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on August 22, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4. |
Wong Mito Lab, |
RCV000851046 | SCV000993280 | benign | MELAS syndrome | 2019-07-12 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.12217A>G variant in MT-TS2 gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished).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 |
Athena Diagnostics | RCV001288304 | SCV001475308 | uncertain significance | not provided | 2020-07-29 | criteria provided, single submitter | clinical testing |