ClinVar Genomic variation as it relates to human health
NM_032578.4(MYPN):c.3583G>A (p.Val1195Met)
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.
Uncertain significance(3); Likely benign(4)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032578.4(MYPN):c.3583G>A (p.Val1195Met)
Variation ID: 31792 Accession: VCV000031792.26
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.3 10: 68201918 (GRCh38) [ NCBI UCSC ] 10: 69961675 (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 4, 2013 May 1, 2024 Mar 26, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032578.4:c.3583G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115967.2:p.Val1195Met missense NM_001256267.2:c.3583G>A NP_001243196.1:p.Val1195Met missense NM_001256268.2:c.2701G>A NP_001243197.1:p.Val901Met missense NR_045662.4:n.3120G>A non-coding transcript variant NR_045663.4:n.3657G>A non-coding transcript variant NC_000010.11:g.68201918G>A NC_000010.10:g.69961675G>A NG_032118.1:g.100802G>A LRG_410:g.100802G>A LRG_410t1:c.3583G>A LRG_410p1:p.Val1195Met Q86TC9:p.Val1195Met - Protein change
- V1195M, V901M
- Other names
- p.V1195M:GTG>ATG
- Canonical SPDI
- NC_000010.11:68201917:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- unknown functional consequence
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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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0.00060 (A)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
The Genome Aggregation Database (gnomAD), exomes 0.00025
Exome Aggregation Consortium (ExAC) 0.00026
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00031
1000 Genomes Project 0.00060
1000 Genomes Project 30x 0.00062
Trans-Omics for Precision Medicine (TOPMed) 0.00075
The Genome Aggregation Database (gnomAD) 0.00083
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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MYPN | - | - |
GRCh38 GRCh37 |
1558 | 1607 |
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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Likely benign (4) |
criteria provided, single submitter
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May 28, 2020 | RCV000024485.8 | |
Conflicting interpretations of pathogenicity (3) |
criteria provided, conflicting classifications
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Jan 22, 2024 | RCV000043543.16 | |
Conflicting interpretations of pathogenicity (2) |
criteria provided, conflicting classifications
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Dec 17, 2023 | RCV000219549.8 | |
Likely benign (1) |
criteria provided, single submitter
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Apr 10, 2019 | RCV000621596.3 | |
Uncertain significance (1) |
criteria provided, single submitter
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Mar 26, 2024 | RCV003989299.1 |
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. |
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Likely benign
(May 28, 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: SCV000236067.12
First in ClinVar: Jul 05, 2015 Last updated: Mar 08, 2017 |
Comment:
This variant is associated with the following publications: (PMID: 22892539, 22337857, 23299917, 18006477, 27896284)
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Likely benign
(Dec 17, 2023)
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criteria provided, single submitter
Method: clinical testing
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not specified
Affected status: unknown
Allele origin:
germline
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Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV004241220.1
First in ClinVar: Feb 04, 2024 Last updated: Feb 04, 2024 |
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Likely benign
(Jan 22, 2024)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1KK
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000814868.7
First in ClinVar: Oct 10, 2018 Last updated: Feb 20, 2024 |
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Uncertain significance
(Mar 26, 2024)
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criteria provided, single submitter
Method: clinical testing
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MYPN-related myopathy
Affected status: unknown
Allele origin:
germline
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Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center
Accession: SCV004807274.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
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Likely benign
(Apr 10, 2019)
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criteria provided, single submitter
Method: clinical testing
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Cardiovascular phenotype
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV000736229.5
First in ClinVar: Apr 14, 2018 Last updated: May 01, 2024 |
Comment:
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of … (more)
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
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Uncertain significance
(Apr 27, 2019)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1KK
Affected status: yes
Allele origin:
unknown
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000930499.1
First in ClinVar: Aug 04, 2019 Last updated: Aug 04, 2019 |
Geographic origin: Iran
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Uncertain significance
(May 18, 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: SCV000272186.3
First in ClinVar: May 29, 2016 Last updated: Apr 09, 2018 |
Comment:
The p.Val1195Met variant in MYPN has been reported in at least 2 individuals wit h DCM (Duboscq-Bidot 2008, LMM data). It has been reported in … (more)
The p.Val1195Met variant in MYPN has been reported in at least 2 individuals wit h DCM (Duboscq-Bidot 2008, LMM data). It has been reported in ClinVar (Variant I D: 31792) with conflicting interpretations. This variant has also been identifie d in 0.2% (53/24012) of African chromosomes by the Genome Aggregation Database ( gnomAD, http://gnomad.broadinstitute.org; dbSNP rs71534280). Computational predi ction tools and conservation analysis suggest that this variant may impact the p rotein, though this information is not predictive enough to determine pathogenic ity. A single in vitro functional study reports that the p.Val1195Met variant ma y impact protein function (Duboscq-Bidot 2008). However, these types of assays m ay not accurately represent biological function. In summary, the clinical signif icance of the p.Val1195Met variant is uncertain. (less)
Number of individuals with the variant: 2
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Pathogenic
(Jan 01, 2008)
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no assertion criteria provided
Method: literature only
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CARDIOMYOPATHY, DILATED, 1KK
Affected status: not provided
Allele origin:
germline
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OMIM
Accession: SCV000071256.2
First in ClinVar: May 26, 2013 Last updated: Nov 06, 2016 |
Comment on evidence:
In a 58-year-old man with dilated cardiomyopathy (CMD1KK; 615248), Duboscq-Bidot et al. (2008) identified heterozygosity for an A-G transition in exon 18 of the MYPN … (more)
In a 58-year-old man with dilated cardiomyopathy (CMD1KK; 615248), Duboscq-Bidot et al. (2008) identified heterozygosity for an A-G transition in exon 18 of the MYPN gene, resulting in a val1195-to-met (V1195M) substitution at a highly conserved residue in an Ig-1 encoding domain. The mutation was not found in 400 ethnically matched controls. The patient had a left ventricular end-diastolic diameter of 63 mm with an 8-mm interventricular septum and an ejection fraction of 34%; electrocardiogram showed incomplete left bundle branch block as well as left ventricular hypertrophy. Immunofluorescence analysis of transfected rat neonate cardiomyocytes showed sarcomeric apparatus disorganization with the mutant compared to wildtype. (less)
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Likely benign
(-)
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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, Academic Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001917050.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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Likely benign
(-)
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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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Genome Diagnostics Laboratory, University Medical Center Utrecht
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001926413.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021 |
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not provided
(Apr 27, 2012)
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no classification provided
Method: curation
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not specified
Affected status: not provided
Allele origin:
germline
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Leiden Muscular Dystrophy (MYPN)
Accession: SCV000045789.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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Germline Functional Evidence
Functional
Help
The functional consequence of the variant, based on experimental evidence and provided by the submitter. consequence |
Method
Help
A brief description of the method used to determine the functional consequence of the variant. A citation for the method is included, when provided by the submitter. |
Result
Help
A brief description of the result of this method for 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 functional evidence for the germline classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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unknown functional consequence
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Leiden Muscular Dystrophy (MYPN)
Accession: SCV000045789.1
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Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Whole Exome Sequencing Identifies Truncating Variants in Nuclear Envelope Genes in Patients With Cardiovascular Disease. | Haskell GT | Circulation. Cardiovascular genetics | 2017 | PMID: 28611029 |
Analyses of more than 60,000 exomes questions the role of numerous genes previously associated with dilated cardiomyopathy. | Nouhravesh N | Molecular genetics & genomic medicine | 2016 | PMID: 27896284 |
New population-based exome data are questioning the pathogenicity of previously cardiomyopathy-associated genetic variants. | Andreasen C | European journal of human genetics : EJHG | 2013 | PMID: 23299917 |
Novel mutations in the sarcomeric protein myopalladin in patients with dilated cardiomyopathy. | Meyer T | European journal of human genetics : EJHG | 2013 | PMID: 22892539 |
Evaluating pathogenicity of rare variants from dilated cardiomyopathy in the exome era. | Norton N | Circulation. Cardiovascular genetics | 2012 | PMID: 22337857 |
Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy. | Duboscq-Bidot L | Cardiovascular research | 2008 | PMID: 18006477 |
Text-mined citations for rs71534280 ...
HelpRecord last updated May 01, 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.