NM_000256.3(MYBPC3):c.1440_1441delinsC (p.Glu480fs) AND Hypertrophic cardiomyopathy

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Jan 25, 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:: RCV000820226.4

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1440_1441delinsC (p.Glu480fs)]

NM_000256.3(MYBPC3):c.1440_1441delinsC (p.Glu480fs)

Gene:

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

Variant type:

Indel

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000256.3(MYBPC3):c.1440_1441delinsC (p.Glu480fs)

HGVS:

NC_000011.10:g.47342846_47342847delinsG
NG_007667.1:g.14856_14857delinsC
NM_000256.3:c.1440_1441delinsCMANE SELECT
NP_000247.2:p.Glu480fs
LRG_386t1:c.1440_1441delinsC
LRG_386:g.14856_14857delinsC
LRG_386p1:p.Glu480fs
NC_000011.9:g.47364397_47364398delinsG
NC_000011.9:g.47364397_47364398delinsG

Protein change:

E480fs

Links:

dbSNP: rs1595846344

NCBI 1000 Genomes Browser:

rs1595846344

Molecular consequence:

NM_000256.3:c.1440_1441delinsC - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV000960931	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 25, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 19574547, 28492532
SCV000992513	Institute of Human Genetics, University of Wuerzburg	no assertion criteria provided	Likely pathogenic	unknown	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000960931

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 25, 2021)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

SCV000992513

Institute of Human Genetics, University of Wuerzburg

no assertion criteria provided

Likely pathogenic

unknown

clinical testing

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
not provided	unknown	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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000960931.3

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

Description

For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in MYBPC3 are known to be pathogenic (PMID: 19574547). This variant has not been reported in the literature in individuals with MYBPC3-related disease. ClinVar contains an entry for this variant (Variation ID: 662561). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu480Aspfs*8) in the MYBPC3 gene. It is expected to result in an absent or disrupted protein product.

#	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 Institute of Human Genetics, University of Wuerzburg, SCV000992513.1

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

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

Last Updated: Feb 14, 2024

ClinVar

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