This variant is associated with the following publications: (PMID: 26969326, 25262649, 16679490, 22681893, 22952768, 12112664, 30245029)
ClinVar Genomic variation as it relates to human health
NM_000260.4(MYO7A):c.4697C>T (p.Thr1566Met)
Germline
Classification
Help
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.
(12)
Help
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.
Benign/Likely benign
12
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000260.4(MYO7A):c.4697C>T (p.Thr1566Met)
Variation ID: 43254 Accession: VCV000043254.32
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 11q13.5 11: 77199663 (GRCh38) [ NCBI UCSC ] 11: 76910708 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Jul 31, 2016 Oct 20, 2024 Jun 1, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000260.4:c.4697C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000251.3:p.Thr1566Met missense NM_001127180.2:c.4583C>T NP_001120652.1:p.Thr1528Met missense NM_001369365.1:c.4550C>T NP_001356294.1:p.Thr1517Met missense NC_000011.10:g.77199663C>T NC_000011.9:g.76910708C>T NG_009086.2:g.76418C>T LRG_1420:g.76418C>T LRG_1420t1:c.4697C>T LRG_1420p1:p.Thr1566Met Q13402:p.Thr1566Met - Protein change
- T1566M, T1528M, T1517M
- Other names
-
NM_000260.3(MYO7A):c.4697C>T(p.Thr1566Met)
NM_001127180.1(MYO7A):c.4583C>T(p.Thr1528Met)
- Canonical SPDI
- NC_000011.10:77199662:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
-
0.00280 (T)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
1000 Genomes Project 0.00280
1000 Genomes Project 30x 0.00297
Trans-Omics for Precision Medicine (TOPMed) 0.00422
Exome Aggregation Consortium (ExAC) 0.00498
The Genome Aggregation Database (gnomAD), exomes 0.00499
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00500
The Genome Aggregation Database (gnomAD) 0.00512
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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. |
|||
| MYO7A | - | - |
GRCh38 GRCh37 |
4340 | 4351 | |
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. |
|---|---|---|---|---|
| Benign (3) |
criteria provided, multiple submitters, no conflicts
|
Jan 31, 2017 | RCV000036159.13 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000384892.5 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV000325844.5 | |
| Benign/Likely benign (4) |
criteria provided, multiple submitters, no conflicts
|
Jun 1, 2024 | RCV000950207.21 | |
| Benign/Likely benign (2) |
criteria provided, multiple submitters, no conflicts
|
May 31, 2018 | RCV000677317.5 | |
| Benign (1) |
no assertion criteria provided
|
Nov 1, 2019 | RCV001826549.1 |
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
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. |
|
|---|---|---|---|---|---|
|
Benign
(Apr 24, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV000513836.6
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
This variant is associated with the following publications: (PMID: 26969326, 25262649, 16679490, 22681893, 22952768, 12112664, 30245029)
|
|
|
Benign
(May 31, 2018)
|
criteria provided, single submitter
Method: curation
|
Usher syndrome type 1
Affected status: unknown
Allele origin:
unknown
|
SIB Swiss Institute of Bioinformatics
Accession: SCV000803492.1
First in ClinVar: Aug 20, 2018 Last updated: Aug 20, 2018 |
Comment:
This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines … (more)
This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal recessive nonsyndromic hearing loss 2
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000374391.3
First in ClinVar: Dec 06, 2016 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Autosomal dominant nonsyndromic hearing loss 11
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000374390.3
First in ClinVar: Dec 06, 2016 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Apr 27, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
Usher syndrome type 1
Affected status: unknown
Allele origin:
germline
|
Illumina Laboratory Services, Illumina
Accession: SCV000374389.3
First in ClinVar: Dec 06, 2016 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
|
|
|
Likely benign
(Jun 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
CeGaT Center for Human Genetics Tuebingen
Accession: SCV004131127.10
First in ClinVar: Nov 20, 2023 Last updated: Oct 20, 2024 |
Comment:
MYO7A: BP4, BS2
Number of individuals with the variant: 14
|
|
|
Benign
(Jan 31, 2017)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
germline
|
Eurofins Ntd Llc (ga)
Accession: SCV000700567.2
First in ClinVar: Dec 19, 2017 Last updated: May 03, 2018 |
Number of individuals with the variant: 4
Sex: mixed
|
|
|
Benign
(Feb 01, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
not provided
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001096495.6
First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024 |
|
|
|
Likely benign
(-)
|
criteria provided, single submitter
Method: not provided
|
not provided
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005211536.1
First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024 |
|
|
|
Benign
(Sep 03, 2010)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: not provided
Allele origin:
germline
|
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
Accession: SCV000059811.6
First in ClinVar: May 03, 2013 Last updated: May 03, 2018 |
Comment:
Thr1566Met in exon 35 of MYO7A: This variant has been reported in the literature (Cremers 2007, Najera 2002, Roux 2006) and in dbSNP (rs41298747). It … (more)
Thr1566Met in exon 35 of MYO7A: This variant has been reported in the literature (Cremers 2007, Najera 2002, Roux 2006) and in dbSNP (rs41298747). It is not exp ected to have clinical significance due to a common occurrence in controls and t he fact that the Met (methionine) variant at position 1566 is present in other m ammalian species including rat and mouse. (less)
Number of individuals with the variant: 32
|
|
|
Benign
(Oct 30, 2015)
|
criteria provided, single submitter
Method: clinical testing
|
not specified
Affected status: unknown
Allele origin:
unknown
|
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia
Accession: SCV000296901.3
First in ClinVar: Jul 31, 2016 Last updated: Dec 24, 2022 |
|
|
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Benign
(Nov 01, 2019)
|
no assertion criteria provided
Method: clinical testing
|
Usher syndrome type 1B
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002088465.1
First in ClinVar: Feb 13, 2022 Last updated: Feb 13, 2022 |
|
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Comment:
Comment:
This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
MYO7A: BP4, BS2
Comment:
Thr1566Met in exon 35 of MYO7A: This variant has been reported in the literature (Cremers 2007, Najera 2002, Roux 2006) and in dbSNP (rs41298747). It is not exp ected to have clinical significance due to a common occurrence in controls and t he fact that the Met (methionine) variant at position 1566 is present in other m ammalian species including rat and mouse.
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. |
Comment:
This variant is associated with the following publications: (PMID: 26969326, 25262649, 16679490, 22681893, 22952768, 12112664, 30245029)
Comment:
This variant is interpreted as a Benign, for Usher syndrome 1B, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: BP4 => Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.). BS1 => Allele frequency is greater than expected for disorder. BS2 => Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
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, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Comment:
MYO7A: BP4, BS2
Comment:
Thr1566Met in exon 35 of MYO7A: This variant has been reported in the literature (Cremers 2007, Najera 2002, Roux 2006) and in dbSNP (rs41298747). It is not exp ected to have clinical significance due to a common occurrence in controls and t he fact that the Met (methionine) variant at position 1566 is present in other m ammalian species including rat and mouse.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Development of a genotyping microarray for Usher syndrome. | Cremers FP | Journal of medical genetics | 2007 | PMID: 16963483 |
| 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 |
| Mutations in myosin VIIA (MYO7A) and usherin (USH2A) in Spanish patients with Usher syndrome types I and II, respectively. | Nájera C | Human mutation | 2002 | PMID: 12112664 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=MYO7A | - | - | - | - |
Text-mined citations for rs41298747 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Oct 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.