rs11659820

Variant names:

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_003803.4(MYOM1):c.1392G>A(p.Arg464Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 1,609,800 control chromosomes in the GnomAD database, including 35,415 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.21 ( 3510 hom., cov: 33)

Exomes 𝑓: 0.20 ( 31905 hom. )

Consequence

MYOM1
NM_003803.4 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.573

Publications

10 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BP6

Variant 18-3164387-C-T is Benign according to our data. Variant chr18-3164387-C-T is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 226800.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.263 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 38	ENST00000356443.9	NP_003794.3	P52179-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MYOM1	ENST00000356443.9 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 38	1	NM_003803.4	ENSP00000348821.4		P52179-1
MYOM1	ENST00000261606.11 link	c.1392G>A	p.Arg464Arg	synonymous_variant	Exon 10 of 37	1		ENSP00000261606.7		P52179-2

Frequencies

GnomAD3 genomes

AF:

0.210

AC:

31880

AN:

152084

Hom.:

3497

Cov.:

show subpopulations

Gnomad AFR

AF:

0.266

Gnomad AMI

AF:

0.286

Gnomad AMR

AF:

0.192

Gnomad ASJ

AF:

0.197

Gnomad EAS

AF:

0.00519

Gnomad SAS

AF:

0.170

Gnomad FIN

AF:

0.138

Gnomad MID

AF:

0.301

Gnomad NFE

AF:

0.208

Gnomad OTH

AF:

0.216

GnomAD2 exomes

AF:

0.180

AC:

43521

AN:

242424

AF XY:

0.181

show subpopulations

Gnomad AFR exome

AF:

0.264

Gnomad AMR exome

AF:

0.154

Gnomad ASJ exome

AF:

0.191

Gnomad EAS exome

AF:

0.00534

Gnomad FIN exome

AF:

0.148

Gnomad NFE exome

AF:

0.210

Gnomad OTH exome

AF:

0.193

GnomAD4 exome

AF:

0.204

AC:

296877

AN:

1457598

Hom.:

31905

Cov.:

AF XY:

0.203

AC XY:

147231

AN XY:

724694

show subpopulations

African (AFR)

AF:

0.270

AC:

9036

AN:

33438

American (AMR)

AF:

0.157

AC:

6935

AN:

44112

Ashkenazi Jewish (ASJ)

AF:

0.191

AC:

4968

AN:

26012

East Asian (EAS)

AF:

0.00449

AC:

178

AN:

39642

South Asian (SAS)

AF:

0.180

AC:

15376

AN:

85492

European-Finnish (FIN)

AF:

0.149

AC:

7932

AN:

53240

Middle Eastern (MID)

AF:

0.209

AC:

1205

AN:

5764

European-Non Finnish (NFE)

AF:

0.216

AC:

239670

AN:

1109618

Other (OTH)

AF:

0.192

AC:

11577

AN:

60280

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

12005

24010

36014

48019

60024

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8294

16588

24882

33176

41470

<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:

0.210

AC:

31929

AN:

152202

Hom.:

3510

Cov.:

AF XY:

0.205

AC XY:

15221

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.267

AC:

11069

AN:

41510

American (AMR)

AF:

0.192

AC:

2930

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.197

AC:

683

AN:

3472

East Asian (EAS)

AF:

0.00520

AC:

AN:

5194

South Asian (SAS)

AF:

0.171

AC:

826

AN:

4818

European-Finnish (FIN)

AF:

0.138

AC:

1467

AN:

10596

Middle Eastern (MID)

AF:

0.299

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.208

AC:

14126

AN:

68002

Other (OTH)

AF:

0.214

AC:

452

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1331

2663

3994

5326

6657

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

332

664

996

1328

1660

<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:

0.212

Hom.:

2327

Bravo

AF:

0.216

Asia WGS

AF:

0.102

AC:

357

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

May 17, 2022

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. -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Arg464Arg in exon 10 of MYOM1: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue and is not located wit hin the splice consensus sequence. It has been identified in 25.2% (1026/4068) o f African American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs11659820). -

not provided

Benign:2

Sep 04, 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

- -

Hypertrophic cardiomyopathy

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

8.8

(source)

DANN

Benign

0.59

PhyloP100

0.57

Mutation Taster

=100/0

polymorphism (auto)

(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

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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