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NM_000256.3(MYBPC3):c.821+1G>A AND Cardiomyopathy

Germline classification:
Pathogenic (2 submissions)
Last evaluated:
Sep 8, 2023
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:
RCV001176299.10

Allele description [Variation Report for NM_000256.3(MYBPC3):c.821+1G>A]

NM_000256.3(MYBPC3):c.821+1G>A

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.821+1G>A
HGVS:
  • NC_000011.10:g.47347856C>T
  • NG_007667.1:g.9847G>A
  • NM_000256.3:c.821+1G>AMANE SELECT
  • LRG_386t1:c.821+1G>A
  • LRG_386:g.9847G>A
  • NC_000011.9:g.47369407C>T
  • c.821+1G>A
Links:
dbSNP: rs397516073
NCBI 1000 Genomes Browser:
rs397516073
Molecular consequence:
  • NM_000256.3:c.821+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]

Condition(s)

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001340216Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 8, 2023) 		germlineclinical testing

PubMed (12)
[See all records that cite these PMIDs]

SCV002042230CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 7, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Mutations in the gene for cardiac myosin-binding protein C and late-onset familial hypertrophic cardiomyopathy.

Niimura H, Bachinski LL, Sangwatanaroj S, Watkins H, Chudley AE, McKenna W, Kristinsson A, Roberts R, Sole M, Maron BJ, Seidman JG, Seidman CE.

N Engl J Med. 1998 Apr 30;338(18):1248-57.

PubMed [citation]
PMID:
9562578

Development of left ventricular hypertrophy in adults in hypertrophic cardiomyopathy caused by cardiac myosin-binding protein C gene mutations.

Maron BJ, Niimura H, Casey SA, Soper MK, Wright GB, Seidman JG, Seidman CE.

J Am Coll Cardiol. 2001 Aug;38(2):315-21.

PubMed [citation]
PMID:
11499718
See all PubMed Citations (12)

Details of each submission

From Color Diagnostics, LLC DBA Color Health, SCV001340216.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (12)

Description

This variant (also known as IVS7+1G>A and as Int8DSG+1A) alters the intron 7 canonical splice donor site of the MYBPC3 gene. Functional RNA studies have shown that this variant causes causes skipping of exon 7, or exons 7 and 8 leading to frameshift and a premature stop codon in exon 9 (PMID: 11499719). This variant has been reported in over 10 unrelated individuals affected with hypertrophic cardiomyopathy (PMID: 9562578, 11499718, 11499719, 21959974, 24510615, 26914223, 27532257, 29121657, 30165862; Color internal data). It has been reported to segregate with disease in multiple affected individuals from two families (PMID: 9562578, 11499719). This variant has also been reported in an infant affected with sudden unexplained death (PMID: 35027292) and in an individual affected with dilated cardiomyopathy (PMID: 35581137). This variant has been identified in 5/172994 chromosomes in the general population by the Genome Aggregation Database (gnomAD). Loss of MYBPC3 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.

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

From CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario, SCV002042230.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 3, 2024