ClinVar Genomic variation as it relates to human health
NM_000257.4(MYH7):c.4844AGA[2] (p.Lys1617del)
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_000257.4(MYH7):c.4844AGA[2] (p.Lys1617del)
Variation ID: 190401 Accession: VCV000190401.37
- Type and length
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Microsatellite, 3 bp
- Location
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Cytogenetic: 14q11.2 14: 23416105-23416107 (GRCh38) [ NCBI UCSC ] 14: 23885314-23885316 (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 Aug 8, 2014 Jul 23, 2024 May 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000257.4:c.4844AGA[2] MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000248.2:p.Lys1617del inframe deletion NM_000257.4:c.4849_4851delAAG MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe deletion NM_000257.4:c.4850_4852del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe deletion NM_000257.4:c.4850_4852delAGA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
inframe deletion NM_000257.2:c.4850_4852del NM_000257.3:c.4850_4852del NR_126491.1:n.368TTC[2] non-coding transcript variant NC_000014.9:g.23416107TTC[2] NC_000014.8:g.23885316TTC[2] NG_007884.1:g.24549AGA[2] LRG_384:g.24549AGA[2] LRG_384t1:c.4850_4852del - Protein change
- K1617del
- Other names
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- Canonical SPDI
- NC_000014.9:23416104:TCTTCTTCTTC:TCTTCTTC
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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.
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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
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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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MYH7 | No evidence available | No evidence available |
GRCh38 GRCh37 |
3627 | 4899 | |
LOC126861897 | - | - | - | GRCh38 | - | 530 |
MHRT | - | - | GRCh38 | - | 783 |
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 (4) |
criteria provided, single submitter
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Oct 18, 2017 | RCV000192202.20 | |
Pathogenic (1) |
criteria provided, single submitter
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Nov 23, 2022 | RCV000526457.15 | |
Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
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May 19, 2024 | RCV000599460.16 | |
Likely pathogenic (1) |
criteria provided, single submitter
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Jul 10, 2021 | RCV001814087.9 |
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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Pathogenic
(Oct 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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MYH7-related skeletal myopathy
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
de novo
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Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München
Accession: SCV000680307.1
First in ClinVar: Feb 08, 2018 Last updated: Feb 08, 2018 |
Sex: male
Tissue: blood
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Pathogenic
(Nov 23, 2022)
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criteria provided, single submitter
Method: clinical testing
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Hypertrophic cardiomyopathy
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000623724.6
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional … (more)
For these reasons, this variant has been classified as Pathogenic. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 190401). This variant has been observed in individuals with autosomal dominant early-onset Laing distal myopathy (PMID: 15322983, 16103042, 24300783, 24664454, 27387980). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This variant, c.4850_4852del, results in the deletion of 1 amino acid(s) of the MYH7 protein (p.Lys1617del), but otherwise preserves the integrity of the reading frame. (less)
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Pathogenic
(May 19, 2024)
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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: SCV000709903.3
First in ClinVar: Apr 02, 2018 Last updated: Jul 23, 2024 |
Comment:
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency … (more)
In-frame deletion of 1 amino acid in a non-repeat region; In silico analysis supports a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 27081534, 24664454, 24300783, 15322983, 27387980, 29660325, 31130284, 32833721, 25214167, 33298082, 31069529) (less)
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Likely pathogenic
(Jul 10, 2021)
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criteria provided, single submitter
Method: clinical testing
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Abnormality of the musculature
Affected status: yes
Allele origin:
germline
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Kariminejad - Najmabadi Pathology & Genetics Center
Accession: SCV001755508.1
First in ClinVar: Jan 22, 2022 Last updated: Jan 22, 2022 |
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Pathogenic
(Nov 17, 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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Revvity Omics, Revvity
Accession: SCV002017674.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Jan 01, 2013)
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no assertion criteria provided
Method: clinical testing
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Myopathy, distal, 1
(Autosomal dominant inheritance)
Affected status: yes
Allele origin:
germline
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Neurogenetics Laboratory, Royal Perth Hospital
Accession: SCV000119904.1
First in ClinVar: Aug 08, 2014 Last updated: Aug 08, 2014 |
Number of individuals with the variant: 18
Family history: Yes
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Pathogenic
(Oct 01, 2004)
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no assertion criteria provided
Method: literature only
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LAING DISTAL MYOPATHY
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000035430.5
First in ClinVar: Apr 04, 2013 Last updated: Mar 18, 2023 |
Comment on evidence:
In affected members of previously reported families with Laing distal myopathy (MPD1; 160500) from Germany (Voit et al., 2001) and mutation. Austria (Zimprich et al., … (more)
In affected members of previously reported families with Laing distal myopathy (MPD1; 160500) from Germany (Voit et al., 2001) and mutation. Austria (Zimprich et al., 2000), Meredith et al. (2004) identified deletion of a lysine at position 1617 in exon 34 of the MYH7 gene. (less)
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not provided
(-)
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no classification provided
Method: literature only
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MYH7-related skeletal myopathy
Affected status: unknown
Allele origin:
germline
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GeneReviews
Accession: SCV000223108.3
First in ClinVar: Oct 05, 2015 Last updated: Oct 01, 2022 |
Comment:
Most common recurrent pathogenic variant
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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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Laing Distal Myopathy. | Adam MP | - | 2021 | PMID: 20301606 |
MYH7-related myopathies: clinical, histopathological and imaging findings in a cohort of Italian patients. | Fiorillo C | Orphanet journal of rare diseases | 2016 | PMID: 27387980 |
Novel mutations widen the phenotypic spectrum of slow skeletal/β-cardiac myosin (MYH7) distal myopathy. | Lamont PJ | Human mutation | 2014 | PMID: 24664454 |
Exome sequencing identifies Laing distal myopathy MYH7 mutation in a Roma family previously diagnosed with distal neuronopathy. | Komlósi K | Neuromuscular disorders : NMD | 2014 | PMID: 24300783 |
Laing early onset distal myopathy: slow myosin defect with variable abnormalities on muscle biopsy. | Lamont PJ | Journal of neurology, neurosurgery, and psychiatry | 2006 | PMID: 16103042 |
Mutations in the slow skeletal muscle fiber myosin heavy chain gene (MYH7) cause laing early-onset distal myopathy (MPD1). | Meredith C | American journal of human genetics | 2004 | PMID: 15322983 |
Autosomal dominant distal myopathy: further evidence of a chromosome 14 locus. | Voit T | Neuromuscular disorders : NMD | 2001 | PMID: 11166161 |
An autosomal dominant early adult-onset distal muscular dystrophy. | Zimprich F | Muscle & nerve | 2000 | PMID: 11102913 |
Text-mined citations for rs121913648 ...
HelpRecord last updated Sep 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.