ClinVar Genomic variation as it relates to human health
m.1095T>C
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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m.1095T>C
Variation ID: 9631 Accession: VCV000009631.8
- Type and length
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single nucleotide variant, 1 bp
- Location
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MT: 1095 (GRCh38) [ NCBI UCSC ] MT: 1095 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Apr 4, 2013 Dec 12, 2021 Jun 15, 2021 - HGVS
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Nucleotide Protein Molecular
consequenceNC_012920.1:m.1095T>C - Protein change
- Other names
- 1095T-C
- Canonical SPDI
- NC_012920.1:1094:T:C
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
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Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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MT-RNR1 | - | - | GRCh38 | 75 | 78 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
Help
The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (1) |
no assertion criteria provided
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Dec 26, 2008 | RCV000010259.10 | |
Pathogenic (1) |
no assertion criteria provided
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Dec 26, 2008 | RCV000010261.10 | |
Pathogenic (1) |
no assertion criteria provided
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Dec 26, 2008 | RCV000010260.10 | |
Uncertain significance (1) |
criteria provided, single submitter
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Feb 4, 2019 | RCV000035031.13 | |
drug response (1) |
reviewed by expert panel
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Jun 15, 2021 | RCV001787379.9 | |
drug response (1) |
reviewed by expert panel
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Jun 15, 2021 | RCV001787380.9 | |
drug response (1) |
reviewed by expert panel
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Jun 15, 2021 | RCV001787381.9 | |
drug response (1) |
reviewed by expert panel
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Jun 15, 2021 | RCV001787382.9 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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drug response
(Jun 15, 2021)
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reviewed by expert panel
Method: curation
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aminoglycoside antibacterials response - Toxicity
Drug used for
Ototoxicity
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV002031229.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
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drug response
(Jun 15, 2021)
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reviewed by expert panel
Method: curation
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gentamicin response - Toxicity
Drug used for
Ototoxicity
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV002031230.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
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drug response
(Jun 15, 2021)
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reviewed by expert panel
Method: curation
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kanamycin response - Toxicity
Drug used for
Ototoxicity
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV002031231.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
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drug response
(Jun 15, 2021)
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reviewed by expert panel
Method: curation
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streptomycin response - Toxicity
Drug used for
Ototoxicity
Affected status: yes
Allele origin:
germline
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PharmGKB
Accession: SCV002031233.1
First in ClinVar: Dec 12, 2021 Last updated: Dec 12, 2021 |
Comment:
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or … (more)
PharmGKB Level of Evidence 1A: Level 1A clinical annotations describe variant-drug combinations that have variant-specific prescribing guidance available in a current clinical guideline annotation or an FDA-approved drug label annotation. Annotations of drug labels or clinical guidelines must give prescribing guidance for specific variants (e.g. CYP2C9*3, HLA-B*57:01) or provide mapping from defined allele functions to diplotypes and phenotypes to be used as supporting evidence for a level 1A clinical annotation. Level 1A clinical annotations must also be supported by at least one publication in addition to a clinical guideline or drug label with variant-specific prescribing guidance. (less)
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Uncertain significance
(Feb 04, 2019)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000058671.6
First in ClinVar: May 03, 2013 Last updated: Jan 30, 2015 |
Comment:
The m.1095T>C variant has been reported in 24/2455 individuals with hearing loss, with and without aminoglycoside exposure (Thyagarajan 2000, Tessa 2001, Zhao 2004, Wang 2005, … (more)
The m.1095T>C variant has been reported in 24/2455 individuals with hearing loss, with and without aminoglycoside exposure (Thyagarajan 2000, Tessa 2001, Zhao 2004, Wang 2005, Li 2005, Dai 2006, Lu 2010, Shen 2001). In one Italian family with Parkinsonism, deafness and neuropathy, the variant segregated with hearing loss in at least two additional maternally related family members (Thyagaragan 2000), while in another family the variant segregated with nonsyndromic hearing loss in 4 family members (Tessa 2001), though alternate dominant inheritance cannot be ruled out. In addition, two functional studies show that the m.1095T>C variant impacts function (Thyagarajan 2000, Muderman 2012). Furthermore, a meta-analysis from several studies of mitochondrial hearing loss variants detected in hearing loss cohorts suggests that the m.1095T>C variant has a significant association with hearing loss when aminoglycoside exposure was assessed. However, this variant is reported in 0.12% (58/47,412) individuals in a broad population database (https://www.mitomap.org), and was a defining variant of the M11 haplogroup where it is present in 100% of individuals of that haplogroup (Tanaka 2004, Yao 2006). In summary, there is some evidence suggesting that the m.1095T>C variant may be associated with hearing loss, particularly with aminoglycoside exposure, however because of its frequency in the general population and the M11 haplogroup, the clinical significance of this variant is uncertain. ACMG/AMP criteria applied: PS4_Moderate, PP1, PS3_Supporting, BS1_Supporting. (less)
Number of individuals with the variant: 5
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Pathogenic
(Dec 26, 2008)
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no assertion criteria provided
Method: literature only
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DEAFNESS, AMINOGLYCOSIDE-INDUCED
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030483.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). … (more)
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). The predicted effect of the mutation is to destroy the stem-loop secondary structure, resulting in impaired translation. Respiratory chain analysis also revealed a significant decrease of COX activity, which may be a result of impaired mitochondrial translation. Thyagarajan et al. (2000) noted an association in the proband between the mutation and neuropathic symptoms, including parkinsonism, and cited previous studies that had suggested a correlation between mitochondrial COX deficiency and Parkinson disease. Tessa et al. (2001) analyzed 80 deaf children for the presence of deafness-related mtDNA mutations. In 1 child with sudden onset of severe/profound hearing loss across all frequencies and with a medical history of aminoglycoside-induced deafness (580000) in 2 maternal relatives, they found the 1095T-C transition in the 12S rRNA gene. The mutation, which occurs at a highly conserved position of the 12S rRNA gene, was homoplasmic in the proband and less abundant in maternal relatives, and was not found in 100 haplotype-matched controls. Zhao et al. (2004) reported the clinical and sequence analysis of the entire mitochondrial genome in 3 Chinese subjects with aminoglycoside-induced and nonsyndromic hearing impairment. Clinical evaluation showed a variable phenotype of hearing impairment including the age of onset and audiometric configuration in these subjects. All subjects showed the 1095T-C mutation and exhibited distinct sets of mtDNA polymorphisms that may contribute to the phenotypic expression of the 1095T-C mutation. Wang et al. (2005) identified an MTRNR1 1095T-C mutation in a 27-year-old Chinese woman with adult-onset hearing loss due to auditory neuropathy. She had no history of aminoglycoside exposure. By performing a phylogenetic reappraisal of complete mtDNA sequences of the 12S rRNA gene in East Asian patients with aminoglycoside-induced and nonsyndromic hearing loss, Yao et al. (2006) concluded that the 1095T-C mutation actually defines a basal haplotype branch of the East Asian mtDNA phylogeny, and is thus likely nonpathogenic. The authors also presented evidence disputing the pathogenicity of other reported mutations in the 12S rRNA gene associated with hearing loss. Dai et al. (2008) reported a Chinese girl with onset of profound nonsyndromic hearing loss at age 6 months who had both the 1555A-G (561000.0001) and 1095T-C mutations. The authors suggested that the 2 mutations acted together to enhance the biochemical defects resulting in hearing impairment. (less)
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Pathogenic
(Dec 26, 2008)
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no assertion criteria provided
Method: literature only
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DEAFNESS, NONSYNDROMIC SENSORINEURAL, MITOCHONDRIAL
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030484.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). … (more)
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). The predicted effect of the mutation is to destroy the stem-loop secondary structure, resulting in impaired translation. Respiratory chain analysis also revealed a significant decrease of COX activity, which may be a result of impaired mitochondrial translation. Thyagarajan et al. (2000) noted an association in the proband between the mutation and neuropathic symptoms, including parkinsonism, and cited previous studies that had suggested a correlation between mitochondrial COX deficiency and Parkinson disease. Tessa et al. (2001) analyzed 80 deaf children for the presence of deafness-related mtDNA mutations. In 1 child with sudden onset of severe/profound hearing loss across all frequencies and with a medical history of aminoglycoside-induced deafness (580000) in 2 maternal relatives, they found the 1095T-C transition in the 12S rRNA gene. The mutation, which occurs at a highly conserved position of the 12S rRNA gene, was homoplasmic in the proband and less abundant in maternal relatives, and was not found in 100 haplotype-matched controls. Zhao et al. (2004) reported the clinical and sequence analysis of the entire mitochondrial genome in 3 Chinese subjects with aminoglycoside-induced and nonsyndromic hearing impairment. Clinical evaluation showed a variable phenotype of hearing impairment including the age of onset and audiometric configuration in these subjects. All subjects showed the 1095T-C mutation and exhibited distinct sets of mtDNA polymorphisms that may contribute to the phenotypic expression of the 1095T-C mutation. Wang et al. (2005) identified an MTRNR1 1095T-C mutation in a 27-year-old Chinese woman with adult-onset hearing loss due to auditory neuropathy. She had no history of aminoglycoside exposure. By performing a phylogenetic reappraisal of complete mtDNA sequences of the 12S rRNA gene in East Asian patients with aminoglycoside-induced and nonsyndromic hearing loss, Yao et al. (2006) concluded that the 1095T-C mutation actually defines a basal haplotype branch of the East Asian mtDNA phylogeny, and is thus likely nonpathogenic. The authors also presented evidence disputing the pathogenicity of other reported mutations in the 12S rRNA gene associated with hearing loss. Dai et al. (2008) reported a Chinese girl with onset of profound nonsyndromic hearing loss at age 6 months who had both the 1555A-G (561000.0001) and 1095T-C mutations. The authors suggested that the 2 mutations acted together to enhance the biochemical defects resulting in hearing impairment. (less)
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Pathogenic
(Dec 26, 2008)
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no assertion criteria provided
Method: literature only
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AUDITORY NEUROPATHY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000030485.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
Comment on evidence:
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). … (more)
Thyagarajan et al. (2000) identified a 1095T-C mutation in the 12SrRNA gene in 3 members of a large family with maternally inherited sensorineural deafness (500008). The predicted effect of the mutation is to destroy the stem-loop secondary structure, resulting in impaired translation. Respiratory chain analysis also revealed a significant decrease of COX activity, which may be a result of impaired mitochondrial translation. Thyagarajan et al. (2000) noted an association in the proband between the mutation and neuropathic symptoms, including parkinsonism, and cited previous studies that had suggested a correlation between mitochondrial COX deficiency and Parkinson disease. Tessa et al. (2001) analyzed 80 deaf children for the presence of deafness-related mtDNA mutations. In 1 child with sudden onset of severe/profound hearing loss across all frequencies and with a medical history of aminoglycoside-induced deafness (580000) in 2 maternal relatives, they found the 1095T-C transition in the 12S rRNA gene. The mutation, which occurs at a highly conserved position of the 12S rRNA gene, was homoplasmic in the proband and less abundant in maternal relatives, and was not found in 100 haplotype-matched controls. Zhao et al. (2004) reported the clinical and sequence analysis of the entire mitochondrial genome in 3 Chinese subjects with aminoglycoside-induced and nonsyndromic hearing impairment. Clinical evaluation showed a variable phenotype of hearing impairment including the age of onset and audiometric configuration in these subjects. All subjects showed the 1095T-C mutation and exhibited distinct sets of mtDNA polymorphisms that may contribute to the phenotypic expression of the 1095T-C mutation. Wang et al. (2005) identified an MTRNR1 1095T-C mutation in a 27-year-old Chinese woman with adult-onset hearing loss due to auditory neuropathy. She had no history of aminoglycoside exposure. By performing a phylogenetic reappraisal of complete mtDNA sequences of the 12S rRNA gene in East Asian patients with aminoglycoside-induced and nonsyndromic hearing loss, Yao et al. (2006) concluded that the 1095T-C mutation actually defines a basal haplotype branch of the East Asian mtDNA phylogeny, and is thus likely nonpathogenic. The authors also presented evidence disputing the pathogenicity of other reported mutations in the 12S rRNA gene associated with hearing loss. Dai et al. (2008) reported a Chinese girl with onset of profound nonsyndromic hearing loss at age 6 months who had both the 1555A-G (561000.0001) and 1095T-C mutations. The authors suggested that the 2 mutations acted together to enhance the biochemical defects resulting in hearing impairment. (less)
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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PharmGKB summary: very important pharmacogene information for MT-RNR1. | Barbarino JM | Pharmacogenetics and genomics | 2016 | PMID: 27654872 |
Mitochondrial mutations associated with aminoglycoside ototoxicity and hearing loss susceptibility identified by meta-analysis. | Jing W | Journal of medical genetics | 2015 | PMID: 25515069 |
The mitochondrial T1095C mutation increases gentamicin-mediated apoptosis. | Muyderman H | Mitochondrion | 2012 | PMID: 22735573 |
The prevalence of mitochondrial mutations associated with aminoglycoside-induced sensorineural hearing loss in an NICU population. | Ealy M | The Laryngoscope | 2011 | PMID: 21495045 |
Frequency and spectrum of mitochondrial 12S rRNA variants in 440 Han Chinese hearing impaired pediatric subjects from two otology clinics. | Shen Z | Journal of translational medicine | 2011 | PMID: 21205314 |
Mitochondrial 12S rRNA variants in 1642 Han Chinese pediatric subjects with aminoglycoside-induced and nonsyndromic hearing loss. | Lu J | Mitochondrion | 2010 | PMID: 20100600 |
Co-segregation of the T1095C with the A1555G mutation of the mitochondrial 12S rRNA gene in a patient with non-syndromic hearing loss. | Dai D | Biochemical and biophysical research communications | 2008 | PMID: 18983818 |
Frequency of mitochondrial 12S ribosomal RNA variants in an adult cystic fibrosis population. | Conrad DJ | Pharmacogenetics and genomics | 2008 | PMID: 18830133 |
Molecular analysis of mitochondrial gene mutations in Korean patients with nonsyndromic hearing loss. | Bae JW | International journal of molecular medicine | 2008 | PMID: 18636170 |
Extremely low penetrance of deafness associated with the mitochondrial 12S rRNA T1095C mutation in three Chinese families. | Dai P | Biochemical and biophysical research communications | 2006 | PMID: 16875663 |
A reappraisal of complete mtDNA variation in East Asian families with hearing impairment. | Yao YG | Human genetics | 2006 | PMID: 16528519 |
Mutational analysis of the mitochondrial 12S rRNA gene in Chinese pediatric subjects with aminoglycoside-induced and non-syndromic hearing loss. | Li Z | Human genetics | 2005 | PMID: 15841390 |
Clinical and molecular characterization of a Chinese patient with auditory neuropathy associated with mitochondrial 12S rRNA T1095C mutation. | Wang Q | American journal of medical genetics. Part A | 2005 | PMID: 15637703 |
Clinical evaluation and sequence analysis of the complete mitochondrial genome of three Chinese patients with hearing impairment associated with the 12S rRNA T1095C mutation. | Zhao L | Biochemical and biophysical research communications | 2004 | PMID: 15555598 |
Mitochondrial genome variation in eastern Asia and the peopling of Japan. | Tanaka M | Genome research | 2004 | PMID: 15466285 |
Maternally inherited deafness associated with a T1095C mutation in the mDNA. | Tessa A | European journal of human genetics : EJHG | 2001 | PMID: 11313749 |
A novel mitochondrial 12SrRNA point mutation in parkinsonism, deafness, and neuropathy. | Thyagarajan D | Annals of neurology | 2000 | PMID: 11079536 |
https://www.pharmgkb.org/clinicalAnnotation/1444699743 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451436133 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451436138 | - | - | - | - |
https://www.pharmgkb.org/clinicalAnnotation/1451436140 | - | - | - | - |
https://www.pharmgkb.org/variant/PA166158908 | - | - | - | - |
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Text-mined citations for rs267606618 ...
HelpRecord last updated Apr 20, 2024
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.