ClinVar Genomic variation as it relates to human health
NM_000260.4(MYO7A):c.2283-1G>T
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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NM_000260.4(MYO7A):c.2283-1G>T
Variation ID: 43178 Accession: VCV000043178.19
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.5 11: 77179044 (GRCh38) [ NCBI UCSC ] 11: 76890090 (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 May 29, 2016 Feb 14, 2024 Nov 7, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000260.4:c.2283-1G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
splice acceptor NM_001127180.2:c.2283-1G>T splice acceptor NM_001369365.1:c.2250-1G>T splice acceptor NC_000011.10:g.77179044G>T NC_000011.9:g.76890090G>T NG_009086.2:g.55799G>T LRG_1420:g.55799G>T LRG_1420t1:c.2283-1G>T NP_000251.3:p.Ser762CysfsTer61 - Protein change
- Other names
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- Canonical SPDI
- NC_000011.10:77179043:G:T
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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.
Trans-Omics for Precision Medicine (TOPMed) 0.00001
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
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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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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MYO7A | - | - |
GRCh38 GRCh37 |
4296 | 4307 |
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
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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 (2) |
criteria provided, single submitter
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Jan 3, 2022 | RCV000036082.6 | |
Pathogenic (1) |
criteria provided, single submitter
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May 30, 2018 | RCV000666504.1 | |
Pathogenic (1) |
criteria provided, single submitter
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Mar 20, 2012 | RCV000844717.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 13, 2019 | RCV001329739.1 | |
Pathogenic (4) |
criteria provided, multiple submitters, no conflicts
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Nov 7, 2023 | RCV001383209.9 | |
Pathogenic (1) |
no assertion criteria provided
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Apr 2, 2021 | RCV001831630.1 |
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
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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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Pathogenic
(Mar 20, 2012)
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criteria provided, single submitter
Method: clinical testing
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Rare genetic deafness
(Autosomal recessive inheritance)
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059734.6
First in ClinVar: May 03, 2013 Last updated: Aug 31, 2019 |
Comment:
The c.2283-1G>T variant in MYO7A has been reported in 8 probands with Usher synd rome (Roux 2011, Bonnet 2011, Jaijo 2011, Roux 2006). 6/8 of … (more)
The c.2283-1G>T variant in MYO7A has been reported in 8 probands with Usher synd rome (Roux 2011, Bonnet 2011, Jaijo 2011, Roux 2006). 6/8 of these probands were homozygous and 2/8 compound heterozygous. The variant segregated with the disea se in one family and it was absent from 200 control chromosomes (Jaijo 2011). Th e variant alters the invariant region of the 3' splice sequence which leads to s kipping of exon 20, as shown by the analysis of the RNA (Jaijo 2011). In summar y, this variant meets our criteria to be classified as pathogenic for autosomal recessive Usher syndrome. (less)
Number of individuals with the variant: 4
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Pathogenic
(Nov 07, 2023)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV001582289.4
First in ClinVar: May 10, 2021 Last updated: Feb 14, 2024 |
Comment:
This sequence change affects an acceptor splice site in intron 19 of the MYO7A gene. It is expected to disrupt RNA splicing. Variants that disrupt … (more)
This sequence change affects an acceptor splice site in intron 19 of the MYO7A gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in MYO7A are known to be pathogenic (PMID: 8900236, 25404053). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with Usher syndrome (PMID: 16679490, 20497194, 25404053, 25798947, 31479088). ClinVar contains an entry for this variant (Variation ID: 43178). Studies have shown that disruption of this splice site alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 20497194). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(May 30, 2018)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1
Autosomal recessive nonsyndromic hearing loss 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000790809.1
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Pathogenic
(Sep 13, 2019)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 11
Affected status: yes
Allele origin:
unknown
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Baylor Genetics
Accession: SCV001521259.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID: 16679490, 25798947, 20497194, … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as pathogenic [PMID: 16679490, 25798947, 20497194, 25404053, ClinVar ID: 43178] (less)
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Pathogenic
(Nov 24, 2020)
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criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV001811922.1
First in ClinVar: Sep 08, 2021 Last updated: Sep 08, 2021 |
Comment:
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., … (more)
Canonical splice site variant in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 33576163, 31589614, 31479088, 27583663, 27440999, 20301442, 21569298, 21436283, 16679490, 25798947, 25404053, 20497194, 23647439, 24498627, 17361009, 25560255) (less)
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Pathogenic
(Jan 03, 2022)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1
Affected status: yes
Allele origin:
germline
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3billion
Accession: SCV002059054.1
First in ClinVar: Jan 15, 2022 Last updated: Jan 15, 2022 |
Comment:
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are … (more)
Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through protein truncation. Multiple pathogenic variants are reported in the predicted truncated region (PVS1_VS).The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000043178, 3billion dataset). It is not observed in the gnomAD v2.1.1 dataset (PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Clinical Features:
Hearing impairment (present) , Visual impairment (present)
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001969914.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001957663.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Apr 02, 2021)
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no assertion criteria provided
Method: clinical testing
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Usher syndrome type 1B
Affected status: unknown
Allele origin:
germline
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Natera, Inc.
Accession: SCV002086607.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
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not provided
(-)
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no classification provided
Method: literature only
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Usher syndrome type 1
Affected status: yes
Allele origin:
germline
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GeneReviews
Accession: SCV000268742.2
First in ClinVar: May 29, 2016 Last updated: Oct 01, 2022 |
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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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PHENOTYPIC CHARACTERISTICS OF ROD-CONE DYSTROPHY ASSOCIATED WITH MYO7A MUTATIONS IN A LARGE FRENCH COHORT. | Khateb S | Retina (Philadelphia, Pa.) | 2020 | PMID: 31479088 |
Usher Syndrome Type I. | Adam MP | - | 2020 | PMID: 20301442 |
Whole exome sequencing identifies mutations in Usher syndrome genes in profoundly deaf Tunisian patients. | Riahi Z | PloS one | 2015 | PMID: 25798947 |
Targeted next generation sequencing for molecular diagnosis of Usher syndrome. | Aparisi MJ | Orphanet journal of rare diseases | 2014 | PMID: 25404053 |
Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis. | Bonnet C | Orphanet journal of rare diseases | 2011 | PMID: 21569298 |
Four-year follow-up of diagnostic service in USH1 patients. | Roux AF | Investigative ophthalmology & visual science | 2011 | PMID: 21436283 |
Functional analysis of splicing mutations in MYO7A and USH2A genes. | Jaijo T | Clinical genetics | 2011 | PMID: 20497194 |
Survey of the frequency of USH1 gene mutations in a cohort of Usher patients shows the importance of cadherin 23 and protocadherin 15 genes and establishes a detection rate of above 90%. | Roux AF | Journal of medical genetics | 2006 | PMID: 16679490 |
Splicing in action: assessing disease causing sequence changes. | Baralle D | Journal of medical genetics | 2005 | PMID: 16199547 |
Myosin VIIA mutation screening in 189 Usher syndrome type 1 patients. | Weston MD | American journal of human genetics | 1996 | PMID: 8900236 |
Text-mined citations for rs397516295 ...
HelpRecord last updated Jul 29, 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.