rs200728597

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

This summary comes from the ClinGen Evidence Repository: The filtering allele frequency of the c.5736C>T (p.Ile1912=) variant in the MYH7 gene is 0.36% (72/16512) of South Asian chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). LINK:https://erepo.genome.network/evrepo/ui/classification/CA016427/MONDO:0004994/002

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00032 ( 7 hom. )

Consequence

MYH7
NM_000257.4 synonymous

Scores

Clinical Significance

Benign reviewed by expert panel B:15

Conservation

PhyloP100: -1.33

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BA1

For more information check the summary or visit ClinGen Evidence Repository.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYH7	NM_000257.4 link	c.5736C>T	p.Ile1912Ile	synonymous_variant	Exon 39 of 40	ENST00000355349.4	NP_000248.2	P12883
MYH7	NM_001407004.1 link	c.5736C>T	p.Ile1912Ile	synonymous_variant	Exon 38 of 39		NP_001393933.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYH7	ENST00000355349.4 link	c.5736C>T	p.Ile1912Ile	synonymous_variant	Exon 39 of 40	1	NM_000257.4	ENSP00000347507.3		P12883

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152254

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00435

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000478

GnomAD3 exomes

AF:

0.000624

AC:

157

AN:

251460

Hom.:

AF XY:

0.000883

AC XY:

120

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000109

Gnomad SAS exome

AF:

0.00454

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.0000879

Gnomad OTH exome

AF:

0.000651

GnomAD4 exome

AF:

0.000324

AC:

473

AN:

1461888

Hom.:

Cov.:

AF XY:

0.000446

AC XY:

324

AN XY:

727244

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00430

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.0000567

Gnomad4 OTH exome

AF:

0.000546

GnomAD4 genome

AF:

0.000158

AC:

AN:

152372

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74510

show subpopulations

Gnomad4 AFR

AF:

0.0000240

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00435

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000473

Alfa

AF:

0.0000675

Hom.:

Bravo

AF:

0.0000378

EpiCase

AF:

0.0000545

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: reviewed by expert panel

LINK: link

Submissions by phenotype

not provided

Benign:6

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

May 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

MYH7: BP4, BP7 -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Likely benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Cardiomyopathy

Benign:4

Dec 24, 2018

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 18, 2023

All of Us Research Program, National Institutes of Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Oct 16, 2018

Color Diagnostics, LLC DBA Color Health

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Dec 15, 2016

ClinGen Cardiomyopathy Variant Curation Expert Panel

Significance: Benign

Review Status: reviewed by expert panel

Collection Method: curation

The filtering allele frequency of the c.5736C>T (p.Ile1912=) variant in the MYH7 gene is 0.36% (72/16512) of South Asian chromosomes by the Exome Aggregation Consortium (http://exac.broadinstitute.org), which is a high enough frequency to be classified as benign based on thresholds defined by the ClinGen Inherited Cardiomyopathy Expert Panel (BA1; PMID:29300372). -

not specified

Benign:3

Jun 25, 2015

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

p.Ile1912Ile in exon 39 of MYH7: This variant is not expected to have clinical s ignificance because it does not alter an amino acid residue, is not located with in the splice consensus sequence, and has been identified in 0.4% (72/16512) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.b roadinstitute.org; dbSNP rs200728597). -

Aug 16, 2018

Eurofins Ntd Llc (ga)

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Hypertrophic cardiomyopathy

Benign:1

Jan 07, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Cardiovascular phenotype

Benign:1

Jul 30, 2023

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

-0.46

CADD

Benign

8.1

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over