NM_000256.3(MYBPC3):c.3491-3C>G AND Cardiovascular phenotype

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 26, 2024
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV002453540.2

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3491-3C>G]

NM_000256.3(MYBPC3):c.3491-3C>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.3491-3C>G

HGVS:

NC_000011.10:g.47332705G>C
NG_007667.1:g.24998C>G
NM_000256.3:c.3491-3C>GMANE SELECT
LRG_386t1:c.3491-3C>G
LRG_386:g.24998C>G
NC_000011.9:g.47354256G>C

Links:

dbSNP: rs730880592

NCBI 1000 Genomes Browser:

rs730880592

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
SCV002612839	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Feb 26, 2024)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25351510, 30645170, 33190526 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002612839

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Feb 26, 2024)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Novel genotype-phenotype associations demonstrated by high-throughput sequencing in patients with hypertrophic cardiomyopathy.

Lopes LR, Syrris P, Guttmann OP, O'Mahony C, Tang HC, Dalageorgou C, Jenkins S, Hubank M, Monserrat L, McKenna WJ, Plagnol V, Elliott PM.

Heart. 2015 Feb;101(4):294-301. doi: 10.1136/heartjnl-2014-306387. Epub 2014 Oct 28.

PubMed [citation]

PMID:: 25351510
PMCID:: PMC4345808

Key Value of RNA Analysis of MYBPC3 Splice-Site Variants in Hypertrophic Cardiomyopathy.

Singer ES, Ingles J, Semsarian C, Bagnall RD.

Circ Genom Precis Med. 2019 Jan;12(1):e002368. doi: 10.1161/CIRCGEN.118.002368.

PubMed [citation]

PMID:: 30645170

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002612839.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.3491-3C>G intronic variant results from a C to G substitution 3 nucleotides upstream from coding exon 32 in the MYBPC3 gene. This variant was identified in an individual with a personal and family history of hypertrophic cardiomyopathy (HCM); RNA studies in the proband demonstrated exon 32 skipping resulting in a premature protein truncation (Singer ES et al. Circ Genom Precis Med, 2019 01;12:e002368). In addition, this variant has been reported in a HCM cohorts; however, clinical details were limited (Lopes LR et al. Heart, 2015 Feb;101:294-301; O'Hare BJ et al. Circ Genom Precis Med, 2020 Dec;13:e003013). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice acceptor site. Based on the majority of available evidence to date, this variant is likely to be 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

Last Updated: May 7, 2024

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