VCV000926746.14 - ClinVar

NM_000257.4(MYH7):c.3200T>C (p.Met1067Thr)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Uncertain significance

6 out of 6 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.3200T>C (p.Met1067Thr)

Variation ID: 926746 Accession: VCV000926746.14

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q11.2 14: 23422225 (GRCh38) [ NCBI UCSC ] 14: 23891434 (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	Jun 22, 2020	Feb 23, 2026	Dec 3, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_000257.4:c.3200T>C MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000248.2:p.Met1067Thr	missense
NC_000014.9:g.23422225A>G
NC_000014.8:g.23891434A>G
NG_007884.1:g.18437T>C
LRG_384:g.18437T>C
LRG_384t1:c.3200T>C

... more HGVS ... less HGVS

Protein change

M1067T

Other names

Canonical SPDI

NC_000014.9:23422224:A:G

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.

The Genome Aggregation Database (gnomAD), exomes 0.00000

The Genome Aggregation Database (gnomAD), exomes 0.00001

Exome Aggregation Consortium (ExAC) 0.00002

Links

ClinGen: CA036139 dbSNP: rs763564858 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	4371	5888

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.
Cardiomyopathy	Uncertain significance (2)	criteria provided, multiple submitters, no conflicts	Nov 20, 2023	RCV001189553.7
not provided	Uncertain significance (1)	criteria provided, single submitter	Apr 15, 2021	RCV001776136.2
Cardiovascular phenotype	Uncertain significance (1)	criteria provided, single submitter	Nov 6, 2025	RCV002320418.3
Congenital myopathy with fiber type disproportion Dilated cardiomyopathy 1S Hypertrophic cardiomyopathy 1 MYH7-related skeletal myopathy Myopathy, myosin storage, autosomal recessive Myosin storage myopathy	Uncertain significance (1)	criteria provided, single submitter	Oct 11, 2021	RCV002484035.1
Hypertrophic cardiomyopathy	Uncertain significance (1)	criteria provided, single submitter	Dec 3, 2025	RCV005093984.2

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.	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 (Oct 11, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	MYH7-related skeletal myopathy Myosin storage myopathy Hypertrophic cardiomyopathy 1 Myopathy, myosin storage, autosomal recessive Congenital myopathy 4A, autosomal dominant Myosin storage myopathy Dilated cardiomyopathy 1S	Fulgent Genetics, Fulgent Genetics Accession: SCV002785935.1 First in ClinVar: Dec 31, 2022 Last updated: Dec 31, 2022	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: unknown

Uncertain significance (Apr 15, 2021) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV002013398.2 First in ClinVar: Nov 12, 2021 Last updated: Mar 04, 2023	Comment: show Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32815737) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Nov 01, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy	Color Diagnostics, LLC DBA Color Health Accession: SCV001356863.4 First in ClinVar: Jun 22, 2020 Last updated: May 03, 2025	Comment: show This missense variant replaces methionine with threonine at codon 1067 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 2/251484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Platform type: NGS

Uncertain significance (Nov 06, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Cardiovascular phenotype	Ambry Genetics Accession: SCV002610238.3 First in ClinVar: Nov 29, 2022 Last updated: Jan 11, 2026	Publications: PubMed (2) PubMed: 32815737‚ 33762593 Comment: show The p.M1067T variant (also known as c.3200T>C), located in coding exon 23 of the MYH7 gene, results from a T to C substitution at nucleotide position 3200. The methionine at codon 1067 is replaced by threonine, an amino acid with similar properties. This variant was reported in individual(s) with features consistent with hypertrophic cardiomyopathy (HCM) (Pua CJ et al. Circ Genom Precis Med, 2020 Oct;13:424-434). This variant was also reported in an intrauterine fetal demise cohort (Muin DA et al. Sci Rep, 2021 Mar;11:6737). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain Significance (Nov 20, 2023) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cardiomyopathy (Autosomal dominant inheritance)	All of Us Research Program, National Institutes of Health Accession: SCV004835476.1 First in ClinVar: Apr 20, 2024 Last updated: Apr 20, 2024 Comment: This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of … (more) This study involves interpretation of variants in research participants for the purpose of population health screening. Participant phenotype was not available at the time of variant classification. Additional details can be found in publication PMID: 35346344, PMCID: PMC8962531 (less)	Comment: show This missense variant replaces methionine with threonine at codon 1067 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 2/251484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: 1 Single Heterozygote

Uncertain significance (Dec 03, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hypertrophic cardiomyopathy	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV005812392.2 First in ClinVar: Feb 25, 2025 Last updated: Feb 23, 2026	Publications: PubMed (2) PubMed: 32815737‚ 37652022 Comment: show This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1067 of the MYH7 protein (p.Met1067Thr). This variant is present in population databases (rs763564858, gnomAD 0.002%). This missense change has been observed in individual(s) with MYH7-related conditions (PMID: 32815737, 37652022). ClinVar contains an entry for this variant (Variation ID: 926746). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 32815737)

Comment:

This missense variant replaces methionine with threonine at codon 1067 of the MYH7 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH7-related disorders in the literature. This variant has been identified in 2/251484 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

Comment:

The p.M1067T variant (also known as c.3200T>C), located in coding exon 23 of the MYH7 gene, results from a T to C substitution at nucleotide position 3200. The methionine at codon 1067 is replaced by threonine, an amino acid with similar properties. This variant was reported in individual(s) with features consistent with hypertrophic cardiomyopathy (HCM) (Pua CJ et al. Circ Genom Precis Med, 2020 Oct;13:424-434). This variant was also reported in an intrauterine fetal demise cohort (Muin DA et al. Sci Rep, 2021 Mar;11:6737). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.

Comment:

This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 1067 of the MYH7 protein (p.Met1067Thr). This variant is present in population databases (rs763564858, gnomAD 0.002%). This missense change has been observed in individual(s) with MYH7-related conditions (PMID: 32815737, 37652022). ClinVar contains an entry for this variant (Variation ID: 926746). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt MYH7 protein function with a positive predictive value of 95%. 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.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
The penetrance of rare variants in cardiomyopathy-associated genes: A cross-sectional approach to estimating penetrance for secondary findings.	McGurk KA	American journal of human genetics	2023	PMID: 37652022
Cardio-pathogenic variants in unexplained intrauterine fetal death: a retrospective pilot study.	Muin DA	Scientific reports	2021	PMID: 33762593
Genetic Studies of Hypertrophic Cardiomyopathy in Singaporeans Identify Variants in TNNI3 and TNNT2 That Are Common in Chinese Patients.	Pua CJ	Circulation. Genomic and precision medicine	2020	PMID: 32815737

Text-mined citations for rs763564858 ...

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 13, 2026