ClinVar Miner

Submissions for variant m.12811T>C

dbSNP: rs199974018
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen RCV003319177 SCV004023281 benign Mitochondrial disease 2023-04-17 reviewed by expert panel curation The m.12811T>C (p. Y159H) variant in MT-ND5 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on April 17, 2023. This variant has not been reported in the medical literature as an individual cause of primary mitochondrial disease to our knowledge. However, there are nine cases reported that have this variant and the common Leber Hereditary Optic Neuropathy (LHON) variant, m.11778G>A, and one case with this variant and the m.3460G>A common LHON variant (PMIDs: 17406640, 17434142, 19026397). While this variant has been reported to be a modifier or secondary variant for LHON, assessment of such variants is outside the scope of this curation. The computational predictor APOGEE gives a consensus rating of 0.32 (Min=0, Max=1), supporting a neutral effect of this variant on function (BP4). This variant is present in population databases including MITOMAP’s GenBank sequences (674/59,389; 1.135%), in the Helix dataset (1,274/195,983; 0.650%; includes 1274 homoplasmic occurrences and 14 heteroplasmic occurrences and seen in haplogroups H, M, A, K, W, D, L2, T), and in gnomAD v3.1.2 (328/56,429; 0.581%; includes 328 homoplasmic occurrences across individuals of East Asian, European (non-Finnish), Latino, and South Asian descent; BA1). 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 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 April 17, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP4, BA1.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000507393 SCV000604441 uncertain significance not provided 2018-03-17 criteria provided, single submitter clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000854857 SCV000997902 benign Leigh syndrome 2019-10-17 criteria provided, single submitter clinical testing The NC_012920.1:m.12811T>C (YP_003024036.1:p.Tyr1159His) variant in MTND5 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BA1
GeneReviews RCV000055698 SCV000086617 not provided Leber optic atrophy no assertion provided literature only

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