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NM_000256.3(MYBPC3):c.3330+5G>C AND Primary familial hypertrophic cardiomyopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 19, 2020
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:
RCV001193928.2

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3330+5G>C]

NM_000256.3(MYBPC3):c.3330+5G>C

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.3330+5G>C
HGVS:
  • NC_000011.10:g.47333189C>G
  • NG_007667.1:g.24514G>C
  • NM_000256.3:c.3330+5G>CMANE SELECT
  • LRG_386t1:c.3330+5G>C
  • LRG_386:g.24514G>C
  • NC_000011.9:g.47354740C>G
  • c.3330+5G>C
Links:
dbSNP: rs373746463
NCBI 1000 Genomes Browser:
rs373746463
Molecular consequence:
  • NM_000256.3:c.3330+5G>C - intron variant - [Sequence Ontology: SO:0001627]

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
SCV001363103Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Oct 19, 2020) 		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 the cardiac myosin binding protein-C gene on chromosome 11 cause familial hypertrophic cardiomyopathy.

Watkins H, Conner D, Thierfelder L, Jarcho JA, MacRae C, McKenna WJ, Maron BJ, Seidman JG, Seidman CE.

Nat Genet. 1995 Dec;11(4):434-7.

PubMed [citation]
PMID:
7493025

Somatic MYH7, MYBPC3, TPM1, TNNT2 and TNNI3 mutations in sporadic hypertrophic cardiomyopathy.

Núñez L, Gimeno-Blanes JR, Rodríguez-García MI, Monserrat L, Zorio E, Coats C, McGregor CG, Hernandez del Rincón JP, Castro-Beiras A, Hermida-Prieto M.

Circ J. 2013;77(9):2358-65. Epub 2013 Jun 19.

PubMed [citation]
PMID:
23782526
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001363103.2

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

Description

Variant summary: MYBPC3 c.3330+5G>C alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. Several computational tools predict a significant impact on normal splicing: Two predict the variant abolishes a 5 splicing donor site and two predict it weakens a 5' donor site. At least two publications report experimental evidence that this variant affects mRNA splicing (Watkins_1995, Ito_2017). The variant allele was found at a frequency of 1.8e-05 in 227264 control chromosomes (gnomAD and publication). c.3330+5G>C has been reported in the literature in multiple individuals affected with Hypertrophic Cardiomyopathy (e.g. Watkins_1995, Nunez_2013, Captur_2014, Miller_2017), including a large family in which the variant segregated with the disease (Watkins_1995). These data indicate that the variant is very likely to be associated with disease. Nine ClinVar submitters (evaluation after 2014) cite the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Oct 13, 2024