NM_000256.3(MYBPC3):c.1483C>T (p.Arg495Trp) AND Cardiomyopathy

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Apr 1, 2022
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:: RCV000770365.4

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1483C>T (p.Arg495Trp)]

NM_000256.3(MYBPC3):c.1483C>T (p.Arg495Trp)

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.1483C>T (p.Arg495Trp)

HGVS:

NC_000011.10:g.47342719G>A
NG_007667.1:g.14984C>T
NM_000256.3:c.1483C>TMANE SELECT
NP_000247.2:p.Arg495Trp
LRG_386t1:c.1483C>T
LRG_386:g.14984C>T
LRG_386p1:p.Arg495Trp
NC_000011.9:g.47364270G>A

Protein change:

R495W

Links:

dbSNP: rs397515905

NCBI 1000 Genomes Browser:

rs397515905

Molecular consequence:

NM_000256.3:c.1483C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

Recent activity

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NADH dehydrogenase subunit 2 (mitochondrion) [Lamprotornis caudatus]
NADH dehydrogenase subunit 2 (mitochondrion) [Lamprotornis caudatus]
gi|149729163|gb|ABR28104.1|

Protein
Abnormal platelet volume
Abnormal platelet volume

MedGen

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000901806	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 1, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004358724	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 5, 2022)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 18713777, 19150014, 20433692, 23283745, 25351510, 27532257, 28356264, 28771489, 31919335, 32492895, 33495597, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000901806

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 1, 2022)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV004358724

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 5, 2022)

germline

clinical testing

PubMed (12)
[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

Hypertrophic cardiomyopathy and athlete's heart: a tale of two entities.

Martín M, Reguero JJ, Castro MG, Coto E, Hernández E, Carro A, Calvo D, de la Tassa CM.

Eur J Echocardiogr. 2009 Jan;10(1):151-3. doi: 10.1093/ejechocard/jen219. Epub 2008 Aug 18.

PubMed [citation]

PMID:: 18713777

[Mutations in sarcomeric genes MYH7, MYBPC3, TNNT2, TNNI3, and TPM1 in patients with hypertrophic cardiomyopathy].

García-Castro M, Coto E, Reguero JR, Berrazueta JR, Alvarez V, Alonso B, Sainz R, Martín M, Morís C.

Rev Esp Cardiol. 2009 Jan;62(1):48-56. Spanish.

PubMed [citation]

PMID:: 19150014

See all PubMed Citations (12)

Details of each submission

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario - Canadian Open Genetics Repository, SCV000901806.2

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Color Diagnostics, LLC DBA Color Health, SCV004358724.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (12)

Description

This missense variant is located in the Ig-like domain C3 of the MYBPC3 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in at least 10 unrelated individuals affected with hypertrophic cardiomyopathy and in a few asymptomatic relatives (PMID: 18713777, 19150014, 20433692, 23283745, 25351510, 27532257, 28356264, 28771489, 31919335, 32492895, 33495597). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Different missense variants occurring at this codon, p.Arg495Gln and p.Arg495Gly, are known to be pathogenic (ClinVar variation ID: 164113, 42537), indicating that arginine at this position is important for the MYBPC3 protein function. Based on the available evidence, this variant is classified as Likely 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: Oct 13, 2024

ClinVar

Relating variation to medicine