ClinVar Miner

Submissions for variant NC_012920.1:m.3243A>G (rs199474657)

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Total submissions: 18
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000224855 SCV000605443 pathogenic not provided 2017-05-12 criteria provided, single submitter clinical testing The m.3243A>G variant (rs199474657) disrupts the mitochondrial tRNA for leucine (UUR), and is one of the most common pathogenic variants in the mitochondrial genome. The clinical presentation associated with this variant is highly variable and depends on the total percentage of abnormal mitochondria and tissue-specific distribution. The m.3243A>G variant was initially identified in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome (Goto 1990), and recent epidemiological studies found that the most frequent presentation is maternally inherited diabetes and deafness (Mancuso 2013, and Nesbitt 2013). Other clinical manifestations include hypertrophic cardiomyopathy, ataxia, basal-ganglia calcifications, and ophthalmoplegia (Gerbitz 1993 and Majamaa 1998).
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224855 SCV000280725 pathogenic not provided 2014-08-26 criteria provided, single submitter clinical testing
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626561 SCV000747262 pathogenic Sensorineural hearing loss; Short stature; Glucose intolerance; Stroke 2017-01-01 criteria provided, single submitter clinical testing
Donald Williams Parsons Laboratory,Baylor College of Medicine RCV000495738 SCV000599945 pathogenic Mitochondrial diseases 2013-07-31 no assertion criteria provided research This variant has been previously reported as disease-causing. It was an incidental finding in our study, in a 5-year-old female with choroid plexiform carcinoma. There was 23% heteroplasmy detected in blood.
Fulgent Genetics,Fulgent Genetics RCV000763623 SCV000894487 pathogenic Myoclonus with epilepsy with ragged red fibers; Juvenile myopathy, encephalopathy, lactic acidosis AND stroke 2018-10-31 criteria provided, single submitter clinical testing
GeneReviews RCV000143997 SCV000188883 pathogenic Leigh syndrome 2014-04-17 no assertion criteria provided literature only
GeneReviews RCV000192054 SCV000207619 pathogenic Myoclonus with epilepsy with ragged red fibers 2015-01-29 no assertion criteria provided literature only
OMIM RCV000010206 SCV000030429 pathogenic Juvenile myopathy, encephalopathy, lactic acidosis AND stroke 2013-01-01 no assertion criteria provided literature only
OMIM RCV000010208 SCV000030431 pathogenic Muscle stiffness, painful 2013-01-01 no assertion criteria provided literature only
OMIM RCV000010209 SCV000030433 pathogenic Age-related macular degeneration 2 2013-01-01 no assertion criteria provided literature only
OMIM RCV000010210 SCV000030434 pathogenic Cyclical vomiting syndrome 2013-01-01 no assertion criteria provided literature only
OMIM RCV000010211 SCV000030435 pathogenic Hepatic failure, early-onset, and neurologic disorder due to cytochrome C oxidase deficiency 2013-01-01 no assertion criteria provided literature only
OMIM RCV000022901 SCV000044192 pathogenic 3-Methylglutaconic aciduria type 1 2013-01-01 no assertion criteria provided literature only
OMIM RCV000022902 SCV000044193 pathogenic MERRF/MELAS overlap syndrome 2013-01-01 no assertion criteria provided literature only
OMIM RCV000032997 SCV000056776 pathogenic Diabetes-deafness syndrome maternally transmitted 2013-01-01 no assertion criteria provided literature only
Unidad de Genómica Médica UC, Pontificia Universidad Católica de Chile RCV000032997 SCV000899115 pathogenic Diabetes-deafness syndrome maternally transmitted 2012-03-05 criteria provided, single submitter research Maternally Inherited Diabetes and Deafness (MIDD) is caused by mutations in mitochondrial DNA (mtDNA), mainly m.3243A>G. Severity, onset and clinical phenotype of MIDD patients are partially determined by the proportion of mutant mitochondrial DNA copies in each cell and tissue (heteroplasmy). The identification of MIDD allows a corred treatment with insulin avoiding drugs that may interfere with mitochondrial electron chain transport. We estimated the degree of heteroplasmy of the mutation m.3243A>G from blood, saliva, hair root and a muscle biopsy using quantitative PCR (qPCR) in a female adult patient. For this purpose, PCR products were inserted in a vector creating plasmids with 3243A or G. Mutant and wild-type vectors were mixed in different proportions to create a calibration curve used to interpolate heteroplasmy percentages with qPCR threshold cycles. The proportions of m.3243A>G heteroplasmy were 62% (muscle), 14% (saliva), 6% (blood leukocytes) and 3% in hair root. Quantitative analysis of heteroplasmy showed marked variations in different tissues (highest in muscle and lowest in blood). Given the relatively high heteroplasmy found in saliva, this type of biological sample may represent an adequate non-invasive way for assessing the presence of m.3243A>G mutations in epidemiologic studies.
Wellcome Centre for Mitochondrial Research,Newcastle University RCV000495738 SCV000577894 pathogenic Mitochondrial diseases 2017-05-22 no assertion criteria provided clinical testing
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine RCV000010206 SCV000992919 pathogenic Juvenile myopathy, encephalopathy, lactic acidosis AND stroke 2019-07-12 criteria provided, single submitter clinical testing The NC_012920.1:m.3243A>G variant in MT-TL1 gene is interpreted to be a Pathogenic variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: PS3, PS5, PP3

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