NM_000256.3(MYBPC3):c.3791G>T (p.Cys1264Phe) AND Hypertrophic cardiomyopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 25, 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:: RCV003586142.1

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3791G>T (p.Cys1264Phe)]

NM_000256.3(MYBPC3):c.3791G>T (p.Cys1264Phe)

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.3791G>T (p.Cys1264Phe)

Other names:

p.C1264F:TGT>TTT

HGVS:

NC_000011.10:g.47332095C>A
NG_007667.1:g.25608G>T
NM_000256.3:c.3791G>TMANE SELECT
NP_000247.2:p.Cys1264Phe
LRG_386t1:c.3791G>T
LRG_386:g.25608G>T
LRG_386p1:p.Cys1264Phe
NC_000011.9:g.47353646C>A
Q14896:p.Cys1264Phe

Protein change:

C1264F; CYS1264PHE

Links:

UniProtKB: Q14896#VAR_070455; OMIM: 600958.0025; dbSNP: rs397514751

NCBI 1000 Genomes Browser:

rs397514751

Molecular consequence:

NM_000256.3:c.3791G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004294779	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 25, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20215591, 29121657, 33782553, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004294779

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 25, 2023)

germline

clinical testing

PubMed (4)
[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

Coding sequence rare variants identified in MYBPC3, MYH6, TPM1, TNNC1, and TNNI3 from 312 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Norton N, Morales A, Li D, Siegfried JD, Gonzalez-Quintana J.

Circ Cardiovasc Genet. 2010 Apr;3(2):155-61. doi: 10.1161/CIRCGENETICS.109.912345. Epub 2010 Mar 9.

PubMed [citation]

PMID:: 20215591
PMCID:: PMC2908892

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 (4)

Details of each submission

From Invitae, SCV004294779.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with phenylalanine, which is neutral and non-polar, at codon 1264 of the MYBPC3 protein (p.Cys1264Phe). This variant is not present in population databases (gnomAD no frequency). 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 64613). This missense change has been observed in individual(s) with dilated cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 20215591, 29121657, 33782553).

#	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: May 1, 2024

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