Submissions for variant NC_012920.1(MT-CO3):m.9804G>A

dbSNP: rs200613617

Total submissions: 7

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 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variant in MTCO3 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished).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
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV001196020	SCV001366449	uncertain significance	See cases	2016-01-01	criteria provided, single submitter	clinical testing	This variant was classified as: Uncertain significance. The following ACMG criteria were applied in classifying this variant: PS1,PP3. This variant was detected in mitochondrial heteroplasmy state.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017233	SCV004847371	benign	not specified	2023-11-13	criteria provided, single submitter	clinical testing	The m.9804G>A variant in MT-CO3 is classified as benign because it has been identified in 0.5% (128/25840) of homoplasmic European alleles by gnomAD (http://gnomad.broadinstitute.org). In addition it was found at 95% frequency in the H6c haplogroup. ACMG/AMP Criteria applied: BA1.
OMIM	RCV000010287	SCV000030511	pathogenic	Leber optic atrophy	1993-10-29	no assertion criteria provided	literature only
GeneReviews	RCV000010287	SCV000086642	not provided	Leber optic atrophy		no assertion provided	literature only