rs1962519

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003803.4(MYOM1):c.541T>C(p.Ser181Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.429 in 1,612,490 control chromosomes in the GnomAD database, including 155,065 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.38 ( 12112 hom., cov: 28)

Exomes 𝑓: 0.43 ( 142953 hom. )

Consequence

MYOM1
NM_003803.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.196

Publications

31 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=9.0599656E-7).

BP6

Variant 18-3188978-A-G is Benign according to our data. Variant chr18-3188978-A-G is described in ClinVar as Benign. ClinVar VariationId is 226830.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.801 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MYOM1	NM_003803.4 link	c.541T>C	p.Ser181Pro	missense_variant	Exon 4 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.541T>C	p.Ser181Pro	missense_variant	Exon 4 of 38	1	NM_003803.4	ENSP00000348821.4		P52179-1
MYOM1	ENST00000261606.11 link	c.541T>C	p.Ser181Pro	missense_variant	Exon 4 of 37	1		ENSP00000261606.7		P52179-2

Frequencies

GnomAD3 genomes

AF:

0.378

AC:

56923

AN:

150678

Hom.:

12103

Cov.:

show subpopulations

Gnomad AFR

AF:

0.205

Gnomad AMI

AF:

0.458

Gnomad AMR

AF:

0.392

Gnomad ASJ

AF:

0.395

Gnomad EAS

AF:

0.821

Gnomad SAS

AF:

0.481

Gnomad FIN

AF:

0.490

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.420

Gnomad OTH

AF:

0.374

GnomAD2 exomes

AF:

0.444

AC:

110640

AN:

249218

AF XY:

0.447

show subpopulations

Gnomad AFR exome

AF:

0.197

Gnomad AMR exome

AF:

0.400

Gnomad ASJ exome

AF:

0.392

Gnomad EAS exome

AF:

0.821

Gnomad FIN exome

AF:

0.504

Gnomad NFE exome

AF:

0.417

Gnomad OTH exome

AF:

0.423

GnomAD4 exome

AF:

0.435

AC:

635354

AN:

1461694

Hom.:

142953

Cov.:

AF XY:

0.436

AC XY:

316962

AN XY:

727128

show subpopulations

African (AFR)

AF:

0.201

AC:

6716

AN:

33480

American (AMR)

AF:

0.402

AC:

17975

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.392

AC:

10245

AN:

26134

East Asian (EAS)

AF:

0.832

AC:

33021

AN:

39700

South Asian (SAS)

AF:

0.473

AC:

40816

AN:

86258

European-Finnish (FIN)

AF:

0.502

AC:

26791

AN:

53402

Middle Eastern (MID)

AF:

0.278

AC:

1603

AN:

5768

European-Non Finnish (NFE)

AF:

0.425

AC:

472075

AN:

1111856

Other (OTH)

AF:

0.433

AC:

26112

AN:

60374

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

23622

47245

70867

94490

118112

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14506

29012

43518

58024

72530

<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:

0.378

AC:

56967

AN:

150796

Hom.:

12112

Cov.:

AF XY:

0.383

AC XY:

28128

AN XY:

73532

show subpopulations

African (AFR)

AF:

0.206

AC:

8443

AN:

41062

American (AMR)

AF:

0.392

AC:

5923

AN:

15116

Ashkenazi Jewish (ASJ)

AF:

0.395

AC:

1367

AN:

3458

East Asian (EAS)

AF:

0.822

AC:

4139

AN:

5034

South Asian (SAS)

AF:

0.483

AC:

2303

AN:

4772

European-Finnish (FIN)

AF:

0.490

AC:

5044

AN:

10286

Middle Eastern (MID)

AF:

0.207

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.420

AC:

28478

AN:

67774

Other (OTH)

AF:

0.379

AC:

796

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1584

3168

4751

6335

7919

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

562

1124

1686

2248

2810

<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:

0.412

Hom.:

62382

Bravo

AF:

0.361

TwinsUK

AF:

0.405

AC:

1501

ALSPAC

AF:

0.426

AC:

1641

ESP6500AA

AF:

0.187

AC:

747

ESP6500EA

AF:

0.415

AC:

3467

ExAC

AF:

0.437

AC:

52817

Asia WGS

AF:

0.614

AC:

2132

AN:

3478

EpiCase

AF:

0.402

EpiControl

AF:

0.392

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Feb 07, 2019

Ambry Genetics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This alteration is classified as 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

Ser181Pro in exon 4 of MYOM1: This variant is not expected to have clinical sign ificance because it has been identified in 41.5% (3467/8348) of European America n chromosomes from a broad population by the NHLBI Exome Sequencing Project (htt p://evs.gs.washington.edu/EVS; dbSNP rs1962519). -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 13, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

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

AlphaMissense

Benign

0.33

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.021

T;.;.

Eigen

Benign

-0.45

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.095

LIST_S2

Benign

0.68

T;T;T

MetaRNN

Benign

9.1e-7

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

L;.;L

PhyloP100

0.20

PrimateAI

Benign

0.32

PROVEAN

Benign

-1.3

N;.;N

REVEL

Benign

0.049

Sift

Benign

0.088

T;.;T

Sift4G

Benign

0.20

T;T;T

Polyphen

0.86

P;.;D

Vest4

0.33

MPC

0.18

ClinPred

0.018

GERP RS

1.3

Varity_R

0.25

gMVP

0.061

Mutation Taster

=99/1

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

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