ClinVar Miner

Submissions for variant NC_012920.1:m.1494C>T (rs267606619)

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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PharmGKB RCV000211324 SCV000268278 drug response aminoglycoside antibacterials response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660813 SCV000783052 drug response amikacin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660814 SCV000783053 drug response gentamicin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660815 SCV000783054 drug response kanamycin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660816 SCV000783055 drug response neomycin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660817 SCV000783056 drug response streptomycin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
PharmGKB RCV000660818 SCV000783057 drug response tobramycin response - Toxicity/ADR 2017-05-19 reviewed by expert panel curation PharmGKB Level of Evidence 2B: Annotation for a variant-drug combination with moderate evidence of an association. The association must be replicated but there may be some studies that do not show statistical significance, and/or the effect size may be small.
Medical Genetics Summaries RCV000722075 SCV000853257 drug response Gentamicin response 2018-08-01 criteria provided, single submitter curation Individuals who have the m.1494C > T variant are at risk of gentamicin-induced hearing loss.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV001449811 SCV001653104 likely pathogenic Rare genetic deafness 2020-07-03 criteria provided, single submitter clinical testing The m.1494C>T variant in MTRNR1 has been reported in the homoplasmic state in >20 Asian and 2 Spanish probands with hearing loss ranging from mild to profound, with the majority having reported exposure to aminoglycoside antibiotics (Chen 2007, Ding 2016, Han 2007, Lu 2010, Rodriguez-Ballesteros 2006, Shen 2011, Wang 2006, Zhao 2004, Zhu 2009). Additionally, this variant segregated with hearing loss in many matrilinial relatives; however, a number of matrilinial relatives with the variant were not reported to have hearing loss with an average penetrance of 18% (range 0-77%) among different families (Barbarino 2016). Most of these non-penetrant relatives were reproted to not have aminoglycoside exposure. Additionally, a meta-analysis of case-control and cohort studies identified the variant at a higher frequency in patients with hearing loss who had been treated with aminoglycosides compared to untreated patients with hearing loss (1.1% vs. 0.056%, respectively, p=0.001). Furthermore, the meta-analysis also found that the m.1494C>T variant was associated with hearing loss and aminoglycoside treatment compared with controls (OR = 2.47 (1.04 - 3.91), p=0.001). The 1494T variant was also significantly associated with hearing loss independent of aminoglycoside use ( OR=1.19 (0.18-2.19), p=0.02). However, it should be noted that the confidence interval crossed or was close to 1 (Jing 2015). This variant is also reported in ClinVar by PharmGKB with evidence level 2B, indicating moderate level of an association for variant-drug combination; however without statistical significance and/or small effect sizes (ClinVar Variation ID: 9632) This variant has also been reported in 16% (1/6) of samples from haplogroup A6a, 0.84% (2/239) of samples from haplogroup D4j, and 0.08% (1/1202) of samples from haplogroup J1c (MitoMap; https://www.mitomap.org/MITOMAP). The nucleotide position at m.1494 is highly conserved through species. In summary, while further case-control studies are required to determine the effect size of this allele, the current data supports a classification of likely pathogenic for hearing loss, especially in the context of exposure to aminogylosides.
OMIM RCV000010262 SCV000030486 pathogenic Aminoglycoside-induced deafness 2006-02-10 no assertion criteria provided literature only
OMIM RCV000010263 SCV000030487 pathogenic Deafness, nonsyndromic sensorineural, mitochondrial 2006-02-10 no assertion criteria provided literature only
GeneReviews RCV000010263 SCV000914173 pathogenic Deafness, nonsyndromic sensorineural, mitochondrial 2018-06-14 no assertion criteria provided literature only
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne RCV000010262 SCV000993413 drug response Aminoglycoside-induced deafness 2018-11-08 no assertion criteria provided research

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