VCV000042887.6 - ClinVar

NM_000257.4(MYH7):c.2171T>A (p.Ile724Asn)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Likely pathogenic(1); Uncertain significance(1)

2 out of 2 submissions contributed to this 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.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000257.4(MYH7):c.2171T>A (p.Ile724Asn)

Variation ID: 42887 Accession: VCV000042887.6

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q11.2 14: 23425810 (GRCh38) [ NCBI UCSC ] 14: 23895019 (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	May 29, 2016	Mar 18, 2023	Feb 23, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_000257.4:c.2171T>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000248.2:p.Ile724Asn	missense
NC_000014.9:g.23425810A>T
NC_000014.8:g.23895019A>T
NG_007884.1:g.14852T>A
LRG_384:g.14852T>A
LRG_384t1:c.2171T>A

... more HGVS ... less HGVS

Protein change

I724N

Other names

Canonical SPDI

NC_000014.9:23425809:A:T

Global minor allele frequency (GMAF) Help 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.

Allele frequency Help The frequency of the allele represented by this VCV record.

Links

ClinGen: CA011864 dbSNP: rs397516136 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.
MYH7		No evidence available	No evidence available	GRCh38 GRCh37	4353	5861

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 specified	Uncertain significance (1)	criteria provided, single submitter	Jan 19, 2014	RCV000035774.6
Dilated cardiomyopathy 1S	Likely pathogenic (1)	criteria provided, single submitter	Feb 23, 2023	RCV003152673.3

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.	Expand all rows Collapse all rows 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.
Uncertain significance (Jan 19, 2014) C Contributing to aggregate classification	criteria provided, single submitter (LMM Criteria)	not specified (Autosomal dominant inheritance)	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000059425.6 First in ClinVar: May 03, 2013 Last updated: May 29, 2016	Comment: show proposed classification - variant undergoing re-assessment, contact laboratory (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: not provided more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: not provided Number of individuals with the variant: 1

Likely pathogenic (Feb 23, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Dilated cardiomyopathy 1S	3billion Accession: SCV003841416.1 First in ClinVar: Mar 18, 2023 Last updated: Mar 18, 2023	Publications: PubMed (3) PubMed: 24503780‚ 31983221‚ 29300372 Comment: show The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID: 29300372). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change (PMID: 24503780) and Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline. (less) Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Clinical Features: Primary dilated cardiomyopathy (present) , Ebstein anomaly (present) , Atrial septal defect, ostium secundum type (present) , Global systolic dysfunction (present) , Left ventricular diastolic dysfunction (present) , High-frequency hearing impairment (present)

Comment:

The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported (PMID: 29300372). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.88; 3Cnet: 1.00). Same nucleotide change resulting in same amino acid change (PMID: 24503780) and Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Reevaluating the Genetic Contribution of Monogenic Dilated Cardiomyopathy.	Mazzarotto F	Circulation	2020	PMID: 31983221
Adaptation and validation of the ACMG/AMP variant classification framework for MYH7-associated inherited cardiomyopathies: recommendations by ClinGen's Inherited Cardiomyopathy Expert Panel.	Kelly MA	Genetics in medicine : official journal of the American College of Medical Genetics	2018	PMID: 29300372
The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.	Pugh TJ	Genetics in medicine : official journal of the American College of Medical Genetics	2014	PMID: 24503780

Text-mined citations for rs397516136 ...

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 Apr 20, 2025