ClinVar Genomic variation as it relates to human health
NM_000260.4(MYO7A):c.1817G>A (p.Arg606His)
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.1817G>A (p.Arg606His)
Variation ID: 517357 Accession: VCV000517357.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 11q13.5 11: 77172767 (GRCh38) [ NCBI UCSC ] 11: 76883813 (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 9, 2018 Oct 7, 2023 Jul 19, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000260.4:c.1817G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000251.3:p.Arg606His missense NM_001127180.2:c.1817G>A NP_001120652.1:p.Arg606His missense NM_001369365.1:c.1784G>A NP_001356294.1:p.Arg595His missense NC_000011.10:g.77172767G>A NC_000011.9:g.76883813G>A NG_009086.2:g.49522G>A LRG_1420:g.49522G>A LRG_1420t1:c.1817G>A LRG_1420p1:p.Arg606His - Protein change
- R606H, R595H
- Other names
- NM_000260.3(MYO7A):c.1817G>A(p.Arg606His)
- NM_000260.3(MYO7A):c.1817G>A
- p.Arg606His
- NM_000260.4(MYO7A):c.1817G>A
- Canonical SPDI
- NC_000011.10:77172766:G:A
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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
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The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00003
Exome Aggregation Consortium (ExAC) 0.00015
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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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 |
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Conditions - Germline
Condition
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The condition for this variant-condition (RCV) record in ClinVar. |
Classification
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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
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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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Uncertain significance (1) |
criteria provided, single submitter
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Jul 27, 2017 | RCV000613132.6 | |
Uncertain significance (1) |
reviewed by expert panel
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Jul 19, 2023 | RCV000710344.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Sep 7, 2022 | RCV001043882.5 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001110608.6 | |
Uncertain significance (1) |
criteria provided, single submitter
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Apr 27, 2017 | RCV001110609.6 | |
Uncertain significance (2) |
criteria provided, multiple submitters, no conflicts
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Jan 16, 2020 | RCV001110610.8 | |
Uncertain significance (1) |
no assertion criteria provided
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Sep 16, 2020 | RCV001272496.3 |
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
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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
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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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Uncertain significance
(Jul 19, 2023)
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reviewed by expert panel
Method: curation
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Nonsyndromic genetic hearing loss
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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ClinGen Hearing Loss Variant Curation Expert Panel
Accession: SCV000840541.5
First in ClinVar: Oct 20, 2018 Last updated: Oct 07, 2023 |
Comment:
The c.1817 G>A (NM_000260.4(MYO7A):c.1817G>A (p.Arg606His)) variant in MYO7A is a missense variant predicted to cause substitution of Arginine by Histidine at amino acid 606. The … (more)
The c.1817 G>A (NM_000260.4(MYO7A):c.1817G>A (p.Arg606His)) variant in MYO7A is a missense variant predicted to cause substitution of Arginine by Histidine at amino acid 606. The highest major allele frequency in gnomAD v2.1.1 is 0.00035 (0.035 % or 8/23092 alleles) in the South Asian population (PM2_supporting, BS1, and BA1 not met). The computational predictor REVEL gives a score of 0.832, (which is above the threshold of 0.7), evidence that correlates with impact to MYO7A function (PP3). This variant has been detected in at least one individual with autosomal recessive nonsyndromic genetic hearing loss. This proband was compound heterozygous for the variant and a pathogenic variant, confirmed in trans by parental testing (PM3; 1.0 point; LMM Internal Data). The patient with this variant displayed moderate to severe sensorineural hearing loss, although no vision anomalies or difficulty seeing at night were noted (PP4 not met; LMM Internal Data). In summary, this variant meets the criteria to be classified as uncertain significance for autosomal recessive nonsyndromic genetic deafness, based on the ACMG/AMP criteria applied, as specified by the ClinGen Hearing Loss VCEP: (PP3, PM3; Version 2, 7.19.2023). (less)
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Uncertain significance
(Jul 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: not provided
Allele origin:
germline
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Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000731600.1
First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
Comment:
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg606His variant in MYO7A has been reported in 1 individual with Usher syndrome type I; however, … (more)
Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg606His variant in MYO7A has been reported in 1 individual with Usher syndrome type I; however, this individual also harbored a homozygous CDH23 variant that likely ex plained the disease (Le Quesne Stabej et al. 2012; LOVD https://grenada.lumc.nl/ LOVD2/Usher_montpellier). It has been reported by our laboratory in 1 individual with hearing loss and delayed walking who had a second pathogenic variant on th e other copy of MYO7A. This variant has been identified in 2/14988 European chr omosomes and 1/1622 East Asian chromosomes by the Genome Aggregation Database (g nomAD, http://gnomad.broadinstitute.org; dbSNP rs782311929); however, this frequ ency is not high enough to rule out a pathogenic role. Computational prediction tools and conservation analyses suggest that this variant may impact the protein , though this information is not predictive enough to determine pathogenicity. I n summary, while there is some suspicion for a pathogenic role, the clinical sig nificance of this variant is uncertain. (less)
Number of individuals with the variant: 2
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal recessive nonsyndromic hearing loss 2
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001268067.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Usher syndrome type 1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001268068.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Autosomal dominant nonsyndromic hearing loss 11
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV001268069.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more)
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. (less)
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Uncertain significance
(Jan 16, 2020)
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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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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV001368510.2
First in ClinVar: Jul 04, 2020 Last updated: Dec 12, 2020 |
Comment:
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in … (more)
This variant was classified as: Uncertain significance. The available evidence on this variant's pathogenicity is insufficient or conflicting. The following ACMG criteria were applied in classifying this variant: PP3. (less)
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Uncertain significance
(Sep 07, 2022)
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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: SCV001207649.3
First in ClinVar: Apr 15, 2020 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 606 of the MYO7A protein (p.Arg606His). … (more)
This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 606 of the MYO7A protein (p.Arg606His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with MYO7A-related conditions. ClinVar contains an entry for this variant (Variation ID: 517357). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. (less)
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Uncertain significance
(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: SCV001454568.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 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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Comprehensive sequence analysis of nine Usher syndrome genes in the UK National Collaborative Usher Study. | Le Quesne Stabej P | Journal of medical genetics | 2012 | PMID: 22135276 |
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/afa3b665-0c01-40e2-9432-4938ce1c8bff | - | - | - | - |
Text-mined citations for rs782311929 ...
HelpRecord last updated Dec 25, 2023
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.