NM_000256.3(MYBPC3):c.3190+4C>T AND Hypertrophic cardiomyopathy

Clinical significance:Uncertain significance (Last evaluated: Aug 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000629030.3

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3190+4C>T]

NM_000256.3(MYBPC3):c.3190+4C>T

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.3190+4C>T
HGVS:
  • NC_000011.10:g.47333553G>A
  • NG_007667.1:g.24150C>T
  • NM_000256.3:c.3190+4C>TMANE SELECT
  • LRG_386t1:c.3190+4C>T
  • LRG_386:g.24150C>T
  • NC_000011.9:g.47355104G>A
Links:
dbSNP: rs571457875
NCBI 1000 Genomes Browser:
rs571457875
Molecular consequence:
  • NM_000256.3:c.3190+4C>T - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:
Hypertrophic cardiomyopathy
Identifiers:
MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; OMIM: PS192600; Human Phenotype Ontology: HP:0001639

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000749940Invitaecriteria provided, single submitter
Uncertain significance
(Aug 23, 2020)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Pathogenic variant burden in the ExAC database: an empirical approach to evaluating population data for clinical variant interpretation.

Kobayashi Y, Yang S, Nykamp K, Garcia J, Lincoln SE, Topper SE.

Genome Med. 2017 Feb 6;9(1):13. doi: 10.1186/s13073-017-0403-7.

PubMed [citation]
PMID:
28166811
PMCID:
PMC5295186

Hypertrophic cardiomyopathy clinical phenotype is independent of gene mutation and mutation dosage.

Viswanathan SK, Sanders HK, McNamara JW, Jagadeesan A, Jahangir A, Tajik AJ, Sadayappan S.

PLoS One. 2017;12(11):e0187948. doi: 10.1371/journal.pone.0187948.

PubMed [citation]
PMID:
29121657
PMCID:
PMC5679632
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000749940.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change falls in intron 29 of the MYBPC3 gene. It does not directly change the encoded amino acid sequence of the MYBPC3 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs571457875, ExAC 0.06%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in an individual affected with hypertrophic cardiomyopathy (PMID: 29121657). ClinVar contains an entry for this variant (Variation ID: 181003). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this intronic change change disrupts the consensus splice site (PMID: 28679633). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Jul 7, 2021

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