NM_000256.3(MYBPC3):c.26-2A>G AND Cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Mar 27, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001176811.9

Allele description [Variation Report for NM_000256.3(MYBPC3):c.26-2A>G]

NM_000256.3(MYBPC3):c.26-2A>G

Gene:

MYBPC3:myosin binding protein C3 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000256.3(MYBPC3):c.26-2A>G

HGVS:

NC_000011.10:g.47351507T>C
NG_007667.1:g.6196A>G
NG_122461.1:g.262T>C
NM_000256.3:c.26-2A>GMANE SELECT
LRG_386t1:c.26-2A>G
LRG_386:g.6196A>G
NC_000011.9:g.47373058T>C
c.26-2A>G

Links:

dbSNP: rs376395543

NCBI 1000 Genomes Browser:

rs376395543

Molecular consequence:

NM_000256.3:c.26-2A>G - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001340870	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Mar 27, 2023)	germline	clinical testing	PubMed (9) [See all records that cite these PMIDs] 15519027, 18957093, 21750094, 22267749, 23674513, 24510615, 27532257, 27831900, 25741868
SCV003837608	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 8, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001340870

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Mar 27, 2023)

germline

clinical testing

PubMed (9)
[See all records that cite these PMIDs]

SCV003837608

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

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 8, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy.

Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ.

J Am Coll Cardiol. 2004 Nov 2;44(9):1903-10.

PubMed [citation]

PMID:: 15519027

Adverse events in families with hypertrophic or dilated cardiomyopathy and mutations in the MYBPC3 gene.

Ehlermann P, Weichenhan D, Zehelein J, Steen H, Pribe R, Zeller R, Lehrke S, Zugck C, Ivandic BT, Katus HA.

BMC Med Genet. 2008 Oct 28;9:95. doi: 10.1186/1471-2350-9-95.

PubMed [citation]

PMID:: 18957093
PMCID:: PMC2584029

See all PubMed Citations (9)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001340870.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (9)

Description

This variant causes an A to G nucleotide substitution at the -2 position of intron 1 splice acceptor site of the MYBPC3 gene. Splice site prediction tools predict that this variant may have a significant impact on RNA splicing. Although RNA studies have not been reported, this variant is expected to disrupt RNA splicing and result in an absent or non-functional protein product. This variant has been reported in over 20 individuals affected with hypertrophic cardiomyopathy (PMID: 15519027, 18957093, 21750094, 22267749, 23674513, 24510615, 27532257, 27831900) and has been shown to segregate with disease in 4 individuals from 2 families (communication with en external laboratory; ClinVar SCV000059162.6). This variant has been identified in 7/255378 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV003837608.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 24, 2024

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