VCV000031800.26 - ClinVar

NM_032578.4(MYPN):c.3403C>A (p.Pro1135Thr)

Germline

Classification

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.

(14)

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

criteria provided, multiple submitters, no conflicts

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_032578.4(MYPN):c.3403C>A (p.Pro1135Thr)

Variation ID: 31800 Accession: VCV000031800.26

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 10q21.3 10: 68199485 (GRCh38) [ NCBI UCSC ] 10: 69959242 (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	Apr 4, 2013	Sep 29, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_032578.4:c.3403C>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_115967.2:p.Pro1135Thr	missense
NM_001256267.2:c.3403C>A	NP_001243196.1:p.Pro1135Thr	missense
NM_001256268.2:c.2521C>A	NP_001243197.1:p.Pro841Thr	missense
NR_045662.4:n.2940C>A		non-coding transcript variant
NR_045663.4:n.3477C>A		non-coding transcript variant
NC_000010.11:g.68199485C>A
NC_000010.10:g.69959242C>A
NG_032118.1:g.98369C>A
LRG_410:g.98369C>A
LRG_410t1:c.3403C>A	LRG_410p1:p.Pro1135Thr
	Q86TC9:p.Pro1135Thr

... more HGVS ... less HGVS

Protein change

P1135T, P841T

Other names

p.P1135T:CCA>ACA

Canonical SPDI

NC_000010.11:68199484:C:A

Functional
consequence

The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

probably no functional consequence

Global minor allele
frequency (GMAF)

The 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.

0.34026 (A)

Allele frequency

The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.33791

1000 Genomes Project 0.34026

Trans-Omics for Precision Medicine (TOPMed) 0.38633

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.40589

The Genome Aggregation Database (gnomAD) 0.40619

The Genome Aggregation Database (gnomAD), exomes 0.43199

Exome Aggregation Consortium (ExAC) 0.43228

Links

ClinGen: CA200038

Leiden Muscular Dystrophy (MYPN): MYPN_00012

UniProtKB: Q86TC9#VAR_049913

dbSNP: rs7079481

VarSome

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
Gene	OMIM	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.
MYPN		-	-	GRCh38 GRCh37	1594	1643

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.
not provided	Benign (2)	criteria provided, single submitter	-	RCV000024493.7
not specified	Benign/Likely benign (7)	criteria provided, multiple submitters, no conflicts	Apr 4, 2023	RCV000172772.13
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Jun 16, 2015	RCV000252665.3
Dilated cardiomyopathy 1KK	Benign (3)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV000625362.10
MYPN-related myopathy	Benign (1)	criteria provided, single submitter	Sep 5, 2021	RCV001778667.2

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 (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	not specified Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000051584.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015 Comments (2): The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 589
Benign (Nov 13, 2013)	criteria provided, single submitter (GeneDx Variant Classification (06012015)) Method: clinical testing	not specified Affected status: yes Allele origin: germline	GeneDx Accession: SCV000170635.11 First in ClinVar: Jun 23, 2014 Last updated: May 29, 2016	Comment: This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at … (more) This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (less)
Benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Dilated cardiomyopathy 1KK Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002015964.1 First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021
Benign (Sep 05, 2021)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	MYPN-related myopathy Affected status: no Allele origin: germline	Genome-Nilou Lab Accession: SCV002015965.1 First in ClinVar: Nov 20, 2021 Last updated: Nov 20, 2021
Benign (Jun 16, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000317454.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as 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)
Benign (May 13, 2016)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	not specified Affected status: yes Allele origin: germline	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute Accession: SCV000740632.1 First in ClinVar: May 29, 2016 Last updated: May 29, 2016
Benign (Sep 29, 2017)	criteria provided, single submitter (ACGS Guidelines, 2013) Method: clinical testing	Dilated cardiomyopathy 1KK Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Study: VKGL Data-share Consensus Accession: SCV000745066.1 First in ClinVar: Apr 20, 2018 Last updated: Apr 20, 2018
Benign (Oct 29, 2014)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000269403.3 First in ClinVar: May 29, 2016 Last updated: May 29, 2016	Publications: PubMed (2) PubMed: 18006477‚ 22286171 Comment: p.Pro1135Thr in exon 18 of MYPN: This variant is not expected to have clinical s ignificance because it has been identified in 48% (4116/8600) of … (more) p.Pro1135Thr in exon 18 of MYPN: This variant is not expected to have clinical s ignificance because it has been identified in 48% (4116/8600) of European Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs7079481). (less) Number of individuals with the variant: 389
Likely benign (Apr 04, 2023)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV003928620.1 First in ClinVar: Jun 03, 2023 Last updated: Jun 03, 2023
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Dilated cardiomyopathy 1KK Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001000086.6 First in ClinVar: Dec 17, 2019 Last updated: Feb 20, 2024
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: not provided	not provided (Autosomal recessive inheritance) Affected status: yes Allele origin: germline	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005318821.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	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: SCV001957846.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001925933.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021
not provided (Apr 27, 2012)	no classification provided Method: curation	not specified Affected status: not provided Allele origin: germline	Leiden Muscular Dystrophy (MYPN) Accession: SCV000045797.1 First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013
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Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Comment:

This alteration is classified as 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.

Comment:

p.Pro1135Thr in exon 18 of MYPN: This variant is not expected to have clinical s ignificance because it has been identified in 48% (4116/8600) of European Americ an chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.e du/EVS/; dbSNP rs7079481).

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.
probably no functional consequence			Leiden Muscular Dystrophy (MYPN) Accession: SCV000045797.1

Comment:

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Molecular basis for clinical heterogeneity in inherited cardiomyopathies due to myopalladin mutations.	Purevjav E	Human molecular genetics	2012	PMID: 22286171
Mutations in the Z-band protein myopalladin gene and idiopathic dilated cardiomyopathy.	Duboscq-Bidot L	Cardiovascular research	2008	PMID: 18006477

Text-mined citations for rs7079481 ...

These 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 Sep 29, 2024

ClinVar Genomic variation as it relates to human health

NM_032578.4(MYPN):c.3403C>A (p.Pro1135Thr)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs7079481 ...