ClinVar Genomic variation as it relates to human health
NM_032578.4(MYPN):c.3122T>A (p.Ile1041Asn)
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(2); Likely benign(2)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_032578.4(MYPN):c.3122T>A (p.Ile1041Asn)
Variation ID: 201871 Accession: VCV000201871.18
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 10q21.3 10: 68195496 (GRCh38) [ NCBI UCSC ] 10: 69955253 (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 May 29, 2016 May 1, 2024 May 5, 2023 - HGVS
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Nucleotide Protein Molecular
consequenceNM_032578.4:c.3122T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_115967.2:p.Ile1041Asn missense NM_001256267.2:c.3122T>A NP_001243196.1:p.Ile1041Asn missense NM_001256268.2:c.2240T>A NP_001243197.1:p.Ile747Asn missense NM_032578.2:c.3122T>A NR_045662.4:n.2659T>A non-coding transcript variant NR_045663.4:n.3196T>A non-coding transcript variant NC_000010.11:g.68195496T>A NC_000010.10:g.69955253T>A NG_032118.1:g.94380T>A LRG_410:g.94380T>A LRG_410t1:c.3122T>A LRG_410p1:p.Ile1041Asn - Protein change
- I1041N, I747N
- Other names
- p.I1041N:ATT>AAT
- Canonical SPDI
- NC_000010.11:68195495:T: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
Help
The frequency of the allele represented by this VCV record.
Trans-Omics for Precision Medicine (TOPMed) 0.00008
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
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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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MYPN | - | - |
GRCh38 GRCh37 |
1558 | 1607 |
Conditions - Germline
Condition
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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 (3) |
criteria provided, multiple submitters, no conflicts
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Oct 1, 2022 | RCV000786383.16 | |
Uncertain significance (1) |
criteria provided, single submitter
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Oct 20, 2022 | RCV000234076.17 | |
Uncertain significance (1) |
criteria provided, single submitter
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May 5, 2023 | RCV003165404.9 |
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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Uncertain significance
(Oct 20, 2022)
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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: SCV000291117.9
First in ClinVar: Jul 01, 2016 Last updated: Feb 07, 2023 |
Comment:
This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 1041 of the MYPN protein (p.Ile1041Asn). … (more)
This sequence change replaces isoleucine, which is neutral and non-polar, with asparagine, which is neutral and polar, at codon 1041 of the MYPN protein (p.Ile1041Asn). This variant is present in population databases (rs754227127, gnomAD 0.06%), including at least one homozygous and/or hemizygous individual. This variant has not been reported in the literature in individuals affected with MYPN-related conditions. ClinVar contains an entry for this variant (Variation ID: 201871). 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: "Benign"; 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
(May 05, 2023)
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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: SCV003860016.2
First in ClinVar: Apr 15, 2023 Last updated: May 01, 2024 |
Comment:
The c.3122T>A (p.I1041N) alteration is located in exon 15 (coding exon 14) of the MYPN gene. This alteration results from a T to A substitution … (more)
The c.3122T>A (p.I1041N) alteration is located in exon 15 (coding exon 14) of the MYPN gene. This alteration results from a T to A substitution at nucleotide position 3122, causing the isoleucine (I) at amino acid position 1041 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. (less)
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Likely benign
(Oct 30, 2018)
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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: SCV000236038.10
First in ClinVar: Jul 05, 2015 Last updated: May 29, 2016 |
Comment:
This variant is associated with the following publications: (PMID: 28492532)
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Likely benign
(Oct 01, 2022)
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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: SCV002821513.8
First in ClinVar: Jan 21, 2023 Last updated: Apr 15, 2024 |
Comment:
MYPN: BP4
Number of individuals with the variant: 1
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Uncertain significance
(Aug 31, 2016)
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no assertion criteria provided
Method: provider interpretation
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not provided
Affected status: unknown
Allele origin:
germline
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Stanford Center for Inherited Cardiovascular Disease, Stanford University
Accession: SCV000925191.1
First in ClinVar: Jun 30, 2019 Last updated: Jun 30, 2019 |
Comment:
P.Ile1041Asn (I1041N) in the MYPN gene Given the lack of cases data, relatively high frequency of the variant in a population database, and limited evidence … (more)
P.Ile1041Asn (I1041N) in the MYPN gene Given the lack of cases data, relatively high frequency of the variant in a population database, and limited evidence to show that this gene causes cardiomyopathy, we consider this variant to be of unknown significance and we do not feel it is suitable for diagnosis or assessing risk in healthy relatives ("predictive genetic testing"). This variant has not been reported in the literature. We have seen this variant in one person with isolated VT. Testing was done by Invitae. The Invitae report notes that there is a large physicochemical difference between isoleucine and asparagine, but the isoleucine residue is weakly conserved. In silico algorithms disagree on pathogenicity: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align- GVGD: "Class C0." The I1041N variant was reported online in 19 of 60,658 (0.03%) individuals in the Exome Aggregation Consortium dataset (http://exac.broadinstitute.org/), which currently includes variant calls on ~64,000 individuals of European, African, Latino and Asian descent (as of 5/9/2016). It was present in the homozygous state in 1 individual. Specifically, the variant was observed in 9 of 8,153 South Asian people, one of whom was a homozygote and 10 of non-Finnish European people. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease. Another variant at the same codon, I1041T, was seen in 1 of 3305 Finnish people in ExAC. (less)
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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
HelpThere are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar. |
Text-mined citations for rs754227127 ...
HelpRecord last updated May 08, 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.