NM_000256.3(MYBPC3):c.3330+5G>C AND Cardiovascular phenotype

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 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:: RCV000247970.5

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3330+5G>C]

NM_000256.3(MYBPC3):c.3330+5G>C

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.3330+5G>C

HGVS:

NC_000011.10:g.47333189C>G
NG_007667.1:g.24514G>C
NM_000256.3:c.3330+5G>CMANE SELECT
LRG_386t1:c.3330+5G>C
LRG_386:g.24514G>C
NC_000011.9:g.47354740C>G
c.3330+5G>C

Links:

dbSNP: rs373746463

Molecular consequence:

NM_000256.3:c.3330+5G>C - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000320055	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Dec 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 7493025, 23054336, 25132132, 25611685 Citation Link,
SCV006067067	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Jul 18, 2023)	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

SCV000320055

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Dec 27, 2023)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link,

SCV006067067

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Jul 18, 2023)

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations in the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy.

Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE.

Nat Genet. 1995 Dec;11(4):434-7.

PubMed [citation]

PMID:: 7493025

Uptake of cardiac screening and genetic testing among hypertrophic and dilated cardiomyopathy families.

Miller EM, Wang Y, Ware SM.

J Genet Couns. 2013 Apr;22(2):258-67. doi: 10.1007/s10897-012-9544-4. Epub 2012 Oct 10.

PubMed [citation]

PMID:: 23054336

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV000320055.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

The c.3330+5G>C intronic alteration consists of a G to C substitution 5 nucleotides after coding exon 30 in the MYBPC3 gene. Based on data from gnomAD, the C allele has an overall frequency of 0.003% (7/258400) total alleles studied. The highest observed frequency was 0.031% (7/22340) of African alleles. This variant was reported to cause skipping of exon 30 in lymphocytes from affected individuals and segregated with hypertrophic cardiomyopathy (HCM) in six individuals from three generations in one family (Watkins, 1995). This variant has also been detected in additional unrelated individuals with HCM (Miller, 2013; Alfares, 2015) This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration may weaken the native splice donor site and may result in the creation or strengthening of a novel splice donor site. Based on the available evidence, this alteration 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 Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV006067067.1

#	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	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 12, 2026

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