NM_000256.3(MYBPC3):c.3124_3125insAA (p.Thr1042fs) AND Cardiovascular phenotype

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 2, 2018
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:: RCV002323816.3

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3124_3125insAA (p.Thr1042fs)]

NM_000256.3(MYBPC3):c.3124_3125insAA (p.Thr1042fs)

Gene:

MYBPC3:myosin binding protein C3 [Gene - OMIM - HGNC]

Variant type:

Insertion

Cytogenetic location:

11p11.2

Genomic location:

Preferred name:

NM_000256.3(MYBPC3):c.3124_3125insAA (p.Thr1042fs)

HGVS:

NC_000011.10:g.47333623_47333624insTT
NG_007667.1:g.24080_24081insAA
NM_000256.3:c.3124_3125insAAMANE SELECT
NP_000247.2:p.Thr1042fs
LRG_386t1:c.3124_3125insAA
LRG_386:g.24080_24081insAA
LRG_386p1:p.Thr1042fs
NC_000011.9:g.47355173_47355174insTT
NC_000011.9:g.47355174_47355175insTT
p.Thr1042LysfsX5

Protein change:

T1042fs

Links:

dbSNP: rs1064793202

NCBI 1000 Genomes Browser:

rs1064793202

Molecular consequence:

NM_000256.3:c.3124_3125insAA - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Penta-EF hand domain containing 1 [Mus musculus]
Penta-EF hand domain containing 1 [Mus musculus]
gi|17512472|gb|AAH19191.1|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002607360	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Jul 2, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15519027, 26914223, 9562578 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002607360

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Jul 2, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Citation Link

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

Myosin binding protein C mutations and compound heterozygosity in hypertrophic cardiomyopathy.

Van Driest SL, Vasile VC, Ommen SR, Will ML, Tajik AJ, Gersh BJ, Ackerman MJ.

J Am Coll Cardiol. 2004 Nov 2;44(9):1903-10.

PubMed [citation]

PMID:: 15519027

Evaluation of the Mayo Clinic Phenotype-Based Genotype Predictor Score in Patients with Clinically Diagnosed Hypertrophic Cardiomyopathy.

Murphy SL, Anderson JH, Kapplinger JD, Kruisselbrink TM, Gersh BJ, Ommen SR, Ackerman MJ, Bos JM.

J Cardiovasc Transl Res. 2016 Apr;9(2):153-61. doi: 10.1007/s12265-016-9681-5. Epub 2016 Feb 25.

PubMed [citation]

PMID:: 26914223
PMCID:: PMC4907543

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002607360.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

The c.3124_3125insAA pathogenic mutation, located in coding exon 29 of the MYBPC3 gene, results from an insertion of two nucleotides at position 3124, causing a translational frameshift with a predicted alternate stop codon (p.T1042Kfs*5). This mutation has been reported in multiple individuals with hypertrophic cardiomyopathy (Niimura H et al. N. Engl. J. Med., 1998 Apr;338:1248-57; Van Driest SL et al. J. Am. Coll. Cardiol., 2004 Nov;44:1903-10; Murphy SL et al. J Cardiovasc Transl Res, 2016 Apr;9:153-61). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation.

#	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: Oct 20, 2024

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