ClinVar Genomic variation as it relates to human health
NM_000260.4(MYO7A):c.3476G>T (p.Gly1159Val)
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.3476G>T (p.Gly1159Val)
Variation ID: 43206 Accession: VCV000043206.33
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.5 11: 77184688 (GRCh38) [ NCBI UCSC ] 11: 76895733 (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 Dec 6, 2016 Apr 15, 2024 Jan 22, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000260.4:c.3476G>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000251.3:p.Gly1159Val missense NM_001127180.2:c.3476G>T NP_001120652.1:p.Gly1159Val missense NM_001369365.1:c.3443G>T NP_001356294.1:p.Gly1148Val missense NC_000011.10:g.77184688G>T NC_000011.9:g.76895733G>T NG_009086.2:g.61443G>T LRG_1420:g.61443G>T LRG_1420t1:c.3476G>T LRG_1420p1:p.Gly1159Val - Protein change
- G1159V, G1148V
- Other names
- NM_001127179.2:c.3476G>T
- Canonical SPDI
- NC_000011.10:77184687: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.
Exome Aggregation Consortium (ExAC) 0.00021
The Genome Aggregation Database (gnomAD) 0.00021
The Genome Aggregation Database (gnomAD), exomes 0.00022
Trans-Omics for Precision Medicine (TOPMed) 0.00023
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
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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MYO7A | - | - |
GRCh38 GRCh37 |
4266 | 4277 |
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
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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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Likely pathogenic (1) |
criteria provided, single submitter
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Oct 13, 2016 | RCV000036110.10 | |
Pathogenic/Likely pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Jan 22, 2024 | RCV000312187.23 | |
Likely pathogenic (2) |
no assertion criteria provided
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Oct 30, 2023 | RCV000664879.3 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Sep 4, 2018 | RCV001073977.2 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Aug 15, 2019 | RCV001270103.2 | |
Likely pathogenic (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001272512.2 | |
Pathogenic (1) |
criteria provided, single submitter
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Sep 17, 2021 | RCV002496550.2 |
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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Likely pathogenic
(Sep 04, 2018)
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criteria provided, single submitter
Method: clinical testing
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Retinal dystrophy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV001239543.1
First in ClinVar: Apr 18, 2020 Last updated: Apr 18, 2020 |
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Likely pathogenic
(Aug 15, 2019)
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criteria provided, single submitter
Method: clinical testing
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Hearing loss
Affected status: unknown
Allele origin:
germline
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Knight Diagnostic Laboratories, Oregon Health and Sciences University
Accession: SCV001448929.1
First in ClinVar: Dec 12, 2020 Last updated: Dec 12, 2020 |
Number of individuals with the variant: 1
Sex: female
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Pathogenic
(Sep 17, 2021)
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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 Autosomal dominant nonsyndromic hearing loss 11
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV002807600.1
First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022 |
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Pathogenic
(Jan 22, 2024)
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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: SCV001419975.4
First in ClinVar: Jul 16, 2020 Last updated: Feb 14, 2024 |
Comment:
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1159 of the MYO7A protein (p.Gly1159Val). … (more)
This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1159 of the MYO7A protein (p.Gly1159Val). This variant is present in population databases (rs199897298, gnomAD 0.05%). This missense change has been observed in individual(s) with autosomal recessive nonsyndromic deafness or Usher syndrome (PMID: 21436283, 23208854, 26969326, 27068579). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is also known as c.1019G>T (p.Gly340Val). ClinVar contains an entry for this variant (Variation ID: 43206). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MYO7A protein function with a positive predictive value of 95%. For these reasons, this variant has been classified as Pathogenic. (less)
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Likely pathogenic
(Apr 01, 2023)
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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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CeGaT Center for Human Genetics Tuebingen
Accession: SCV004010103.6
First in ClinVar: Jul 16, 2023 Last updated: Apr 15, 2024 |
Comment:
MYO7A: PM3:Strong, PM1, PM2, PP3
Number of individuals with the variant: 1
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Pathogenic
(Feb 09, 2017)
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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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Eurofins Ntd Llc (ga)
Accession: SCV000705705.2
First in ClinVar: May 29, 2016 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 1
Sex: mixed
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Likely pathogenic
(Oct 13, 2016)
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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: SCV000059762.6
First in ClinVar: May 03, 2013 Last updated: Dec 15, 2018 |
Comment:
The p.Gly1159Val variant in MYO7A has been reported in 9 individuals with hearin g loss (Roux 2011, Schrauwen 2013, LMM data). Four of these individuals … (more)
The p.Gly1159Val variant in MYO7A has been reported in 9 individuals with hearin g loss (Roux 2011, Schrauwen 2013, LMM data). Four of these individuals were co mpound heterozygous with a second pathogenic or likely pathogenic MYO7A variant, with no indication of retinitis pigmentosa associated with Usher syndrome. Anot her with retinitis pigmentosa had a second variant of uncertain significance in MYO7A. This individual also reportedly has LCHAD, which may explain the retiniti s pigmentosa. This variant has been identified in 12/30732 (0.04%) of European c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org; dbSNP rs199897298); however, this frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conserva tion analysis suggest that this variant may impact the protein, though this info rmation is not predictive enough to determine pathogenicity. In summary, althoug h additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive hearing loss. However, it cannot be determined whether this variant causes type 1 Usher syndrome, atyp ical Usher syndrome, or nonsyndromic hearing loss without additional information . (less)
Number of individuals with the variant: 11
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Pathogenic
(May 02, 2022)
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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: SCV000329830.9
First in ClinVar: Dec 06, 2016 Last updated: Mar 04, 2023 |
Comment:
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26486028, … (more)
In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 26486028, 31589614, 26969326, 23208854, 27068579, 21436283, 30245029, 27160483, 32795431) (less)
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Likely pathogenic
(Jan 04, 2017)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 2
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000788903.2
First in ClinVar: Aug 05, 2018 Last updated: Aug 05, 2018 |
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Likely pathogenic
(Oct 30, 2023)
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no assertion criteria provided
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 2
Affected status: yes
Allele origin:
germline
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Zotz-Klimas Genetics Lab, MVZ Zotz Klimas
Accession: SCV004099485.1
First in ClinVar: Nov 04, 2023 Last updated: Nov 04, 2023 |
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Likely pathogenic
(Sep 16, 2020)
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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: SCV001454584.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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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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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: SCV001951762.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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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: SCV001976217.1 First in ClinVar: Oct 07, 2021 Last updated: Oct 07, 2021 |
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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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Advanced diagnostic genetic testing in inherited retinal disease: experience from a single tertiary referral centre in the UK National Health Service. | Khan KN | Clinical genetics | 2017 | PMID: 27160483 |
DNA Diagnostics of Hereditary Hearing Loss: A Targeted Resequencing Approach Combined with a Mutation Classification System. | Sommen M | Human mutation | 2016 | PMID: 27068579 |
Comprehensive genetic testing in the clinical evaluation of 1119 patients with hearing loss. | Sloan-Heggen CM | Human genetics | 2016 | PMID: 26969326 |
Electroretinogram assessment of children with sensorineural hearing loss: implications for screening. | West SK | Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus | 2015 | PMID: 26486028 |
A sensitive and specific diagnostic test for hearing loss using a microdroplet PCR-based approach and next generation sequencing. | Schrauwen I | American journal of medical genetics. Part A | 2013 | PMID: 23208854 |
Four-year follow-up of diagnostic service in USH1 patients. | Roux AF | Investigative ophthalmology & visual science | 2011 | PMID: 21436283 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYO7A | - | - | - | - |
Text-mined citations for rs199897298 ...
HelpRecord last updated Apr 15, 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.