ClinVar Genomic variation as it relates to human health
NM_032578.4(MYPN):c.3124C>T (p.Arg1042Cys)
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(4); Likely benign(3)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032578.4(MYPN):c.3124C>T (p.Arg1042Cys)
Variation ID: 155824 Accession: VCV000155824.41
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.3 10: 68195498 (GRCh38) [ NCBI UCSC ] 10: 69955255 (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 Feb 6, 2015 May 12, 2024 Jan 18, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032578.4:c.3124C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115967.2:p.Arg1042Cys missense NM_001256267.2:c.3124C>T NP_001243196.1:p.Arg1042Cys missense NM_001256268.2:c.2242C>T NP_001243197.1:p.Arg748Cys missense NR_045662.4:n.2661C>T non-coding transcript variant NR_045663.4:n.3198C>T non-coding transcript variant NC_000010.11:g.68195498C>T NC_000010.10:g.69955255C>T NG_032118.1:g.94382C>T LRG_410:g.94382C>T LRG_410t1:c.3124C>T LRG_410p1:p.Arg1042Cys - Protein change
- R1042C, R748C
- Other names
- -
- Canonical SPDI
- NC_000010.11:68195497:C: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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0.00040 (T)
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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) 0.00037
1000 Genomes Project 0.00040
Exome Aggregation Consortium (ExAC) 0.00040
The Genome Aggregation Database (gnomAD), exomes 0.00041
1000 Genomes Project 30x 0.00047
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00023
The Genome Aggregation Database (gnomAD) 0.00034
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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Uncertain significance (1) |
no assertion criteria provided
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Oct 15, 2014 | RCV000143934.2 | |
Conflicting interpretations of pathogenicity (4) |
criteria provided, conflicting classifications
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Jan 18, 2024 | RCV000228976.14 | |
Likely benign (1) |
criteria provided, single submitter
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Feb 9, 2021 | RCV000252987.3 | |
Uncertain significance (4) |
criteria provided, multiple submitters, no conflicts
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Jul 1, 2023 | RCV000421407.21 | |
Likely benign (1) |
criteria provided, single submitter
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Jan 4, 2022 | RCV001824644.1 |
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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Uncertain significance
(Aug 22, 2016)
|
criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1KK
Affected status: yes
Allele origin:
germline
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Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000743690.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Likely benign
(Jan 04, 2022)
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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: SCV002074528.1
First in ClinVar: Feb 12, 2022 Last updated: Feb 12, 2022 |
Comment:
Variant summary: MYPN c.3124C>T (p.Arg1042Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: MYPN c.3124C>T (p.Arg1042Cys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00041 in 251424 control chromosomes (gnomAD). The observed variant frequency is approximately 8-fold of the estimated maximal expected allele frequency for a pathogenic variant in MYPN causing Cardiomyopathy phenotype (5e-05), strongly suggesting that the variant is benign. c.3124C>T has been reported in the literature in individuals affected with Cardiomyopathy, including dilated cardiomyopathy, hypertrophic cardiomyopathy and left ventricular hypertrabeculation (Akinrinade_2015, Miszalski-Jamka_2017, van Lint_2019). These reports do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. A co-occurrence with a pathogenic variant has been reported (TTNI3 c.407G>A, p.Arg136Gln; van Lint_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters have assessed this variant since 2014: one classified the variant as likely benign and five as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. (less)
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Uncertain significance
(Oct 29, 2021)
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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: SCV000536532.6
First in ClinVar: Mar 08, 2017 Last updated: Mar 04, 2023 |
Comment:
Identified in an individual with left ventricular hypertrabeculation who harbored additional cardiogenetic variants (Miszalski-Jamka et al., 2017) and in multiple individuals referred for genetic testing … (more)
Identified in an individual with left ventricular hypertrabeculation who harbored additional cardiogenetic variants (Miszalski-Jamka et al., 2017) and in multiple individuals referred for genetic testing at GeneDx, several of whom also harbored additional cardiogenetic variants; Reported as a variant of uncertain significance and a likely benign variant in ClinVar but additional evidence is not available (ClinVar Variant ID 155824; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 28798025, 30847666) (less)
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Likely benign
(Jan 18, 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: SCV000291118.8
First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024 |
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Likely benign
(Feb 09, 2021)
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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: SCV000319023.7
First in ClinVar: Oct 02, 2016 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
(May 31, 2017)
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criteria provided, single submitter
Method: clinical testing
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Dilated cardiomyopathy 1KK
Affected status: yes
Allele origin:
germline
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Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745064.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Uncertain significance
(Jul 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: SCV001147937.16
First in ClinVar: Feb 03, 2020 Last updated: May 12, 2024 |
Number of individuals with the variant: 1
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Uncertain significance
(-)
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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: SCV001955114.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Uncertain significance
(Oct 15, 2014)
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no assertion criteria provided
Method: clinical testing
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Primary familial hypertrophic cardiomyopathy
Affected status: yes
Allele origin:
germline
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Blueprint Genetics
Accession: SCV000188812.2
First in ClinVar: Sep 07, 2014 Last updated: Feb 06, 2015 |
Number of individuals with the variant: 2
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Uncertain significance
(-)
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no assertion criteria provided
Method: clinical testing
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Dilated cardiomyopathy 1KK
Affected status: yes
Allele origin:
germline
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Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000732958.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Uncertain significance
(-)
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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: SCV001925617.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 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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Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance. | van Lint FHM | Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation | 2019 | PMID: 30847666 |
Novel Genetic Triggers and Genotype-Phenotype Correlations in Patients With Left Ventricular Noncompaction. | Miszalski-Jamka K | Circulation. Cardiovascular genetics | 2017 | PMID: 28798025 |
Genetics and genotype-phenotype correlations in Finnish patients with dilated cardiomyopathy. | Akinrinade O | European heart journal | 2015 | PMID: 26084686 |
Text-mined citations for rs151282801 ...
HelpRecord last updated May 12, 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.