NM_000256.3(MYBPC3):c.1377del (p.Leu460fs) AND Hypertrophic cardiomyopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 8, 2023
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:: RCV000559279.7

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1377del (p.Leu460fs)]

NM_000256.3(MYBPC3):c.1377del (p.Leu460fs)

Gene:

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

Variant type:

Deletion

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000256.3(MYBPC3):c.1377del (p.Leu460fs)

HGVS:

NC_000011.10:g.47342913del
NG_007667.1:g.14793del
NM_000256.3:c.1377delMANE SELECT
NP_000247.2:p.Leu460fs
LRG_386t1:c.1377del
LRG_386:g.14793del
LRG_386p1:p.Leu460fs
NC_000011.9:g.47364461del
NC_000011.9:g.47364461delG
NC_000011.9:g.47364464del
NM_000256.3:c.1377delCMANE SELECT
p.Leu460TrpfsX6

Protein change:

L460fs

Links:

dbSNP: rs786204339

NCBI 1000 Genomes Browser:

rs786204339

Molecular consequence:

NM_000256.3:c.1377del - 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
SCV000623525	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 8, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 19574547, 21165360, 23283745, 23711808, 26090888, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000623525

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 8, 2023)

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	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

Two novel mutations of the MYBPC3 gene identified in Chinese families with hypertrophic cardiomyopathy.

Lin J, Zheng DD, Tao Q, Yang JH, Jiang WP, Yang XJ, Song JP, Jiang TB, Li X.

Can J Cardiol. 2010 Dec;26(10):518-22.

PubMed [citation]

PMID:: 21165360
PMCID:: PMC3006099

See all PubMed Citations (6)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000623525.4

#	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.Leu460Trpfs*6) 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 individuals with hypertrophic cardiomyopathy (PMID: 21165360, 23283745, 23711808, 26090888). It has also been observed to segregate with disease in related individuals. This variant is also known as Pro459fs. ClinVar contains an entry for this variant (Variation ID: 188548). 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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