NM_000257.4:c.1323G>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_000257.4(MYH7):c.1323G>A(p.Thr441Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00017 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. T441T) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00018 ( 0 hom. )

Consequence

MYH7
NM_000257.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -9.82

Publications

3 publications found

Variant links:

Genes affected

MYH7 (HGNC:7577): (myosin heavy chain 7) Muscle myosin is a hexameric protein containing 2 heavy chain subunits, 2 alkali light chain subunits, and 2 regulatory light chain subunits. This gene encodes the beta (or slow) heavy chain subunit of cardiac myosin. It is expressed predominantly in normal human ventricle. It is also expressed in skeletal muscle tissues rich in slow-twitch type I muscle fibers. Changes in the relative abundance of this protein and the alpha (or fast) heavy subunit of cardiac myosin correlate with the contractile velocity of cardiac muscle. Its expression is also altered during thyroid hormone depletion and hemodynamic overloading. Mutations in this gene are associated with familial hypertrophic cardiomyopathy, myosin storage myopathy, dilated cardiomyopathy, and Laing distal myopathy. [provided by RefSeq, May 2022]

MYH7 Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
dilated cardiomyopathy 1S
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
hypertrophic cardiomyopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
hypertrophic cardiomyopathy 1
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: PanelApp Australia, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics
MYH7-related skeletal myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Ambry Genetics
myopathy, myosin storage, autosomal recessive
Inheritance: AR Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
myopathy, myosin storage, autosomal dominant
Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
congenital myopathy 7A, myosin storage, autosomal dominant
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Ebstein anomaly
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
familial isolated dilated cardiomyopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
hyaline body myopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
left ventricular noncompaction
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
arrhythmogenic right ventricular cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
congenital heart disease
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

MYH7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 14-23429039-C-T is Benign according to our data. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr14-23429039-C-T is described in CliVar as Benign/Likely_benign. Clinvar id is 42833.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-9.82 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.1323G>A	p.Thr441Thr	synonymous_variant	Exon 14 of 40	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.1323G>A	p.Thr441Thr	synonymous_variant	Exon 13 of 39		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYH7	ENST00000355349.4 link	c.1323G>A	p.Thr441Thr	synonymous_variant	Exon 14 of 40	1	NM_000257.4	ENSP00000347507.3	P12883
MYH7	ENST00000713768.1 link	c.1323G>A	p.Thr441Thr	synonymous_variant	Exon 14 of 41			ENSP00000519070.1
MYH7	ENST00000713769.1 link	c.1323G>A	p.Thr441Thr	synonymous_variant	Exon 13 of 39			ENSP00000519071.1

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000398

AC:

AN:

251490

AF XY:

0.0000368

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000791

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000183

AC:

268

AN:

1461894

Hom.:

Cov.:

AF XY:

0.000161

AC XY:

117

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0000374

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000221

AC:

246

AN:

1112012

Other (OTH)

AF:

0.000298

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000460

AC:

AN:

152166

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41436

American (AMR)

AF:

0.00

AC:

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5182

South Asian (SAS)

AF:

0.00

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000103

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000113

Hom.:

Bravo

AF:

0.0000680

EpiCase

AF:

0.000382

EpiControl

AF:

0.000119

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

Feb 03, 2009

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 09, 2025

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

BP7 -

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiomyopathy

Benign:3

Nov 21, 2018

Color Diagnostics, LLC DBA Color Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 05, 2024

All of Us Research Program, National Institutes of Health

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jul 15, 2021

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:3

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 04, 2019

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Aug 01, 2020

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jan 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Apr 26, 2016

Ambry Genetics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.018

(source)

DANN

Benign

0.71

PhyloP100

-9.8

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over