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NM_000256.3(MYBPC3):c.1483C>T (p.Arg495Trp) AND Primary familial hypertrophic cardiomyopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
May 13, 2019
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:
RCV001193929.1

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:
Primary familial hypertrophic cardiomyopathy (HCM)
Synonyms:
Hereditary ventricular hypertrophy; Idiopathic hypertrophic subaortic stenosis
Identifiers:
MONDO: MONDO:0024573; MeSH: D024741; MedGen: C0949658; OMIM: PS192600

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001363106Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(May 13, 2019) 		germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

[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

Screening mutations in myosin binding protein C3 gene in a cohort of patients with Hypertrophic Cardiomyopathy.

Rodríguez-García MI, Monserrat L, Ortiz M, Fernández X, Cazón L, Núñez L, Barriales-Villa R, Maneiro E, Veira E, Castro-Beiras A, Hermida-Prieto M.

BMC Med Genet. 2010 Apr 30;11:67. doi: 10.1186/1471-2350-11-67.

PubMed [citation]
PMID:
20433692
PMCID:
PMC2880974
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363106.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: MYBPC3 c.1483C>T (p.Arg495Trp) results in a non-conservative amino acid change located in the Immunoglobulin subtype 2 (IPR003598) domain and Immunoglobulin I-set (IPR013098) domain of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249906 control chromosomes (gnomAD) but has been reported in the literature in individuals affected with Hypertrophic Cardiomyopathy (Garcia-Castro_2009, Coto_2012, Rodriguez-Garcia_2010, Walsh_2017). These data indicate that the variant may be associated with disease. However, this variant was also found in two asymptomatic family members (Garcia-Castro_2009), suggesting incomplete penetrance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Another missense change at this codon has been classified as pathogenic by our laboratory (p.Arg495Gly). Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 25, 2024