NM_000256.3(MYBPC3):c.1483C>G (p.Arg495Gly) AND Cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 26, 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:: RCV001187169.4

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1483C>G (p.Arg495Gly)]

NM_000256.3(MYBPC3):c.1483C>G (p.Arg495Gly)

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>G (p.Arg495Gly)

Other names:

p.R495G:CGG>GGG

HGVS:

NC_000011.10:g.47342719G>C
NG_007667.1:g.14984C>G
NM_000256.3:c.1483C>GMANE SELECT
NP_000247.2:p.Arg495Gly
LRG_386t1:c.1483C>G
LRG_386:g.14984C>G
LRG_386p1:p.Arg495Gly
NC_000011.9:g.47364270G>C
Q14896:p.Arg495Gly
c.1483C>G

Protein change:

R495G

Links:

UniProtKB: Q14896#VAR_045929; dbSNP: rs397515905

NCBI 1000 Genomes Browser:

rs397515905

Molecular consequence:

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

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001353884	Color Diagnostics, LLC DBA Color Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Jan 26, 2023)	germline	clinical testing	PubMed (12) [See all records that cite these PMIDs] 18403758, 19659763, 20624503, 22267749, 22574137, 23140321, 25611685, 26455666, 27532257, 28615295, 34310159, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001353884

Color Diagnostics, LLC DBA Color Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Jan 26, 2023)

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

Shared genetic causes of cardiac hypertrophy in children and adults.

Morita H, Rehm HL, Menesses A, McDonough B, Roberts AE, Kucherlapati R, Towbin JA, Seidman JG, Seidman CE.

N Engl J Med. 2008 May 1;358(18):1899-908. doi: 10.1056/NEJMoa075463. Epub 2008 Apr 9.

PubMed [citation]

PMID:: 18403758
PMCID:: PMC2752150

A child cohort study from southern Italy enlarges the genetic spectrum of hypertrophic cardiomyopathy.

Frisso G, Limongelli G, Pacileo G, Del Giudice A, Forgione L, Calabrò P, Iacomino M, Detta N, Di Fonzo LM, Maddaloni V, Calabrò R, Salvatore F.

Clin Genet. 2009 Jul;76(1):91-101. doi: 10.1111/j.1399-0004.2009.01190.x.

PubMed [citation]

PMID:: 19659763

See all PubMed Citations (12)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001353884.3

#	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 replaces arginine with glycine at codon 495 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 individuals affected with hypertrophic cardiomyopathy (PMID: 18403758, 19659763, 20624503, 22267749, 22574137, 23140321, 25611685, 26455666, 27532257, 28615295, 34310159). Different variants occurring at the same codon, p.Arg495Gln and p.Arg495Trp, are well documented pathogenic mutations (Clinvar variation ID: 164113 and 164114), indicating that arginine at this position is important for MYBPC3 protein function. This variant has been identified in 1/249206 chromosomes in the general population by the Genome Aggregation Database (gnomAD). 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: Sep 29, 2024

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