ClinVar Miner

Submissions for variant m.9804G>A (rs200613617)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000010287 SCV000746364 pathogenic Leber's optic atrophy 2017-12-03 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756352 SCV000884141 uncertain significance not provided 2017-11-21 criteria provided, single submitter clinical testing The m.9804G>A variant (rs200613617) has been reported as a primary pathogenic variant involved in Leber's hereditary optic neuropathy (LOHN; Johns 1993, Dogulu 2001, Savontaus 1995), and as a secondary variant (Matsumoto 1999). Initial studies identified the variant in 4 independent families, while noting its absence from healthy controls (Johns 1993, Dogulu 2001). However, in one family, the m.9804G>A variant was present in 3 asymptomatic family members (Dogulu 2001). This variant has also been previously observed by our laboratory in two patients, one with optic atrophy and one with chronic myoclonic disorder, neither of whom carried other significant variant in the mitochondrial genome or in 108 nuclear-encoded genes with mitochondrial function. This variant is listed in Mitomap with an overall frequency of 0.28%, and is found in the H6c haplogroup with a frequency of 95%. No functional studies have been conducted to determine the impact of the m.9804G>A variant on complex IV function. While it is possible that m.9804G>A is the primary pathogenic variant in this patient, the frequency in the H6c haplogroup suggests that it is unlikely to be pathogenic; however, due to conflicting evidence in the literature, we cannot classify this variant with certainty.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000854582 SCV000997620 benign Leigh syndrome 2019-10-17 criteria provided, single submitter clinical testing The NC_012920.1:m.9804G>A (YP_003024032.1:p.Ala200Thr) variant in MTCO3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2, BP4
OMIM RCV000010287 SCV000030511 pathogenic Leber's optic atrophy 1993-10-29 no assertion criteria provided literature only
GeneReviews RCV000010287 SCV000086642 pathologic Leber's optic atrophy 2013-09-19 no assertion criteria provided curation Converted during submission to Pathogenic.

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