18-3215158-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.66G>C(p.Val22Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0968 in 1,613,430 control chromosomes in the GnomAD database, including 7,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Synonymous variant affecting the same amino acid position (i.e. V22V) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.10 ( 847 hom., cov: 32)

Exomes 𝑓: 0.096 ( 7099 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -1.37

Publications

8 publications found

Variant links:

Genes affected

MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

MYOM1 Gene-Disease associations (from GenCC):

hypertrophic cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

MYOM1 links:

ENSG00000265399 (HGNC:):

ENSG00000265399 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 18-3215158-C-G is Benign according to our data. Variant chr18-3215158-C-G is described in ClinVar as [Benign]. Clinvar id is 226835.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.37 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.168 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.66G>C	p.Val22Val	synonymous_variant	Exon 2 of 38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
MYOM1	ENST00000356443.9 link	c.66G>C	p.Val22Val	synonymous_variant	Exon 2 of 38	1	NM_003803.4	ENSP00000348821.4	P52179-1
MYOM1	ENST00000261606.11 link	c.66G>C	p.Val22Val	synonymous_variant	Exon 2 of 37	1		ENSP00000261606.7	P52179-2
ENSG00000265399	ENST00000580139.1 link	n.198-1834C>G		intron_variant	Intron 2 of 4	2

Frequencies

GnomAD3 genomes

AF:

0.103

AC:

15733

AN:

152070

Hom.:

849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.123

Gnomad AMI

AF:

0.172

Gnomad AMR

AF:

0.0928

Gnomad ASJ

AF:

0.0816

Gnomad EAS

AF:

0.177

Gnomad SAS

AF:

0.120

Gnomad FIN

AF:

0.0924

Gnomad MID

AF:

0.0348

Gnomad NFE

AF:

0.0898

Gnomad OTH

AF:

0.0842

GnomAD2 exomes

AF:

0.0991

AC:

24525

AN:

247512

AF XY:

0.0989

show subpopulations

Gnomad AFR exome

AF:

0.120

Gnomad AMR exome

AF:

0.0724

Gnomad ASJ exome

AF:

0.0891

Gnomad EAS exome

AF:

0.169

Gnomad FIN exome

AF:

0.0973

Gnomad NFE exome

AF:

0.0917

Gnomad OTH exome

AF:

0.0966

GnomAD4 exome

AF:

0.0961

AC:

140397

AN:

1461242

Hom.:

7099

Cov.:

AF XY:

0.0963

AC XY:

70015

AN XY:

726872

show subpopulations

African (AFR)

AF:

0.117

AC:

3903

AN:

33474

American (AMR)

AF:

0.0727

AC:

3246

AN:

44666

Ashkenazi Jewish (ASJ)

AF:

0.0931

AC:

2432

AN:

26116

East Asian (EAS)

AF:

0.183

AC:

7250

AN:

39668

South Asian (SAS)

AF:

0.111

AC:

9537

AN:

86148

European-Finnish (FIN)

AF:

0.100

AC:

5345

AN:

53366

Middle Eastern (MID)

AF:

0.0574

AC:

331

AN:

5768

European-Non Finnish (NFE)

AF:

0.0919

AC:

102195

AN:

1111676

Other (OTH)

AF:

0.102

AC:

6158

AN:

60360

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

6944

13889

20833

27778

34722

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.103

AC:

15736

AN:

152188

Hom.:

847

Cov.:

AF XY:

0.104

AC XY:

7729

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.123

AC:

5116

AN:

41514

American (AMR)

AF:

0.0929

AC:

1420

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.0816

AC:

283

AN:

3470

East Asian (EAS)

AF:

0.177

AC:

916

AN:

5162

South Asian (SAS)

AF:

0.120

AC:

578

AN:

4828

European-Finnish (FIN)

AF:

0.0924

AC:

980

AN:

10610

Middle Eastern (MID)

AF:

0.0340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0897

AC:

6103

AN:

68002

Other (OTH)

AF:

0.0819

AC:

173

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

719

1438

2156

2875

3594

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0757

Hom.:

166

Bravo

AF:

0.103

Asia WGS

AF:

0.154

AC:

536

AN:

3478

EpiCase

AF:

0.0860

EpiControl

AF:

0.0856

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 06, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

not specified

Benign:1

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Val22Val in exon 2 of MYOM1: This variant is not expected to have clinical signi ficance because it does not alter an amino acid residue and is not located withi n the splice consensus sequence. It has been identified in 12.0% (504/4212) of A frican American chromosomes from a broad population by the NHLBI Exome Sequencin g Project (http://evs.gs.washington.edu/EVS; dbSNP rs1662316). -

MYOM1-related disorder

Benign:1

Oct 21, 2019

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Hypertrophic cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Cardiovascular phenotype

Benign:1

Jan 21, 2013

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.17

(source)

DANN

Benign

0.69

PhyloP100

-1.4

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

Details are displayed if max score is > 0.2

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

Publications

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18-3215158-C-G

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