Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003166006 | SCV003915434 | uncertain significance | Mitochondrial disease | 2023-03-28 | reviewed by expert panel | curation | The m.14633A>G (p.M14T) variant in MT-ND6 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on March 28, 2023. There are no individuals or families with this variant reported in the medical literature to our knowledge. There are several occurrences in population databases. This variant is absent in GenBank MITOMAP sequences. It is present in 0.005% of individuals in gnomAD v3.1.2 (two homoplasmic occurrences in individuals of European background and haplogroup HV; one homoplasmic occurrence in an individual of African/African American background and haplogroup L3) and in 0.005% of individuals in the Helix dataset (10 homoplasmic occurrences and two heteroplasmic occurrences). In silico tools (APOGEE) predict this variant to be neutral (score of 0.4, BP4). There are no cybrid, single fiber, or other studies reported for 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/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on March 28, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4. |
ARUP Laboratories, |
RCV000756360 | SCV000884150 | uncertain significance | not provided | 2017-07-18 | criteria provided, single submitter | clinical testing | This variant affects the MT-ND6 gene (c.41T>C; p.Met14Thr) and has not been reported in the medical literature, is not listed in gene-specific variant databases, nor has it been previously identified in our laboratory. It is also absent from population databases such as MITOMAP. The methionine at codon 14 is moderately conserved considering 11 species, and there is a moderate physiochemical difference between methionine and threonine (Alamut software v2.9). Therefore, based on the available information, the clinical significance of the m.14633A>G variant cannot be determined with certainty. |
Wong Mito Lab, |
RCV000855138 | SCV000998188 | likely benign | Leigh syndrome | 2019-10-17 | criteria provided, single submitter | clinical testing | The NC_012920.1:m.14633A>G (YP_003024037.1:p.Met14Thr) variant in MTND6 gene is interpretated to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS4, BP4, BP5, PP7 |