NM_000256.3(MYBPC3):c.1869C>A (p.Cys623Ter) AND Hypertrophic cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 12, 2021
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:: RCV000151111.8

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1869C>A (p.Cys623Ter)]

NM_000256.3(MYBPC3):c.1869C>A (p.Cys623Ter)

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.1869C>A (p.Cys623Ter)

HGVS:

NC_000011.10:g.47341166G>T
NG_007667.1:g.16537C>A
NM_000256.3:c.1869C>AMANE SELECT
NP_000247.2:p.Cys623Ter
LRG_386t1:c.1869C>A
LRG_386:g.16537C>A
LRG_386p1:p.Cys623Ter
NC_000011.9:g.47362717G>T
p.Cys623X

Protein change:

C623*

Links:

dbSNP: rs397515932

NCBI 1000 Genomes Browser:

rs397515932

Molecular consequence:

NM_000256.3:c.1869C>A - nonsense - [Sequence Ontology: SO:0001587]

Observations:

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000198877	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	no assertion criteria provided	Pathogenic (Mar 4, 2013)	germline	clinical testing
SCV003268856	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 12, 2021)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19574547, 21750094, 25611685, 27532257, 33673806, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000198877

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

no assertion criteria provided

Pathogenic
(Mar 4, 2013)

germline

clinical testing

SCV003268856

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 12, 2021)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	2	2	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

Evidence from human myectomy samples that MYBPC3 mutations cause hypertrophic cardiomyopathy through haploinsufficiency.

Marston S, Copeland O, Jacques A, Livesey K, Tsang V, McKenna WJ, Jalilzadeh S, Carballo S, Redwood C, Watkins H.

Circ Res. 2009 Jul 31;105(3):219-22. doi: 10.1161/CIRCRESAHA.109.202440. Epub 2009 Jul 2.

PubMed [citation]

PMID:: 19574547

Novel correlations between the genotype and the phenotype of hypertrophic and dilated cardiomyopathy: results from the German Competence Network Heart Failure.

Waldmüller S, Erdmann J, Binner P, Gelbrich G, Pankuweit S, Geier C, Timmermann B, Haremza J, Perrot A, Scheer S, Wachter R, Schulze-Waltrup N, Dermintzoglou A, Schönberger J, Zeh W, Jurmann B, Brodherr T, Börgel J, Farr M, Milting H, Blankenfeldt W, Reinhardt R, et al.

Eur J Heart Fail. 2011 Nov;13(11):1185-92. doi: 10.1093/eurjhf/hfr074. Epub 2011 Jul 12.

PubMed [citation]

PMID:: 21750094

See all PubMed Citations (6)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000198877.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

Description

proposed classification - variant undergoing re-assessment, contact laboratory

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		2	not provided	2	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003268856.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change creates a premature translational stop signal (p.Cys623*) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with hypertrophic or dilated cardiomyopathy (PMID: 21750094, 25611685, 27532257, 33673806). ClinVar contains an entry for this variant (Variation ID: 164095). For these reasons, this variant has been 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

Last Updated: Sep 29, 2024

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