NM_000256.3(MYBPC3):c.3812G>A (p.Arg1271Gln) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 20, 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:: RCV002365845.2

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3812G>A (p.Arg1271Gln)]

NM_000256.3(MYBPC3):c.3812G>A (p.Arg1271Gln)

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.3812G>A (p.Arg1271Gln)

HGVS:

NC_000011.10:g.47332074C>T
NG_007667.1:g.25629G>A
NM_000256.3:c.3812G>AMANE SELECT
NP_000247.2:p.Arg1271Gln
LRG_386t1:c.3812G>A
LRG_386:g.25629G>A
LRG_386p1:p.Arg1271Gln
NC_000011.9:g.47353625C>T
NC_000011.9:g.47353625C>T

Protein change:

R1271Q

Links:

dbSNP: rs762225417

NCBI 1000 Genomes Browser:

rs762225417

Molecular consequence:

NM_000256.3:c.3812G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002625484	Ambry Genetics	criteria provided, single submitter (Ambry General Variant Classification Scheme_2022)	Uncertain significance (Apr 20, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30297972, 32841044 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002625484

Ambry Genetics

criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)

Uncertain significance
(Apr 20, 2023)

germline

clinical testing

PubMed (2)
[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

Genotype and Lifetime Burden of Disease in Hypertrophic Cardiomyopathy: Insights from the Sarcomeric Human Cardiomyopathy Registry (SHaRe).

Ho CY, Day SM, Ashley EA, Michels M, Pereira AC, Jacoby D, Cirino AL, Fox JC, Lakdawala NK, Ware JS, Caleshu CA, Helms AS, Colan SD, Girolami F, Cecchi F, Seidman CE, Sajeev G, Signorovitch J, Green EM, Olivotto I.

Circulation. 2018 Oct 2;138(14):1387-1398. doi: 10.1161/CIRCULATIONAHA.117.033200. Epub 2018 Aug 23.

PubMed [citation]

PMID:: 30297972
PMCID:: PMC6170149

Spatial and Functional Distribution of MYBPC3 Pathogenic Variants and Clinical Outcomes in Patients With Hypertrophic Cardiomyopathy.

Helms AS, Thompson AD, Glazier AA, Hafeez N, Kabani S, Rodriguez J, Yob JM, Woolcock H, Mazzarotto F, Lakdawala NK, Wittekind SG, Pereira AC, Jacoby DL, Colan SD, Ashley EA, Saberi S, Ware JS, Ingles J, Semsarian C, Michels M, Olivotto I, Ho CY, et al.

Circ Genom Precis Med. 2020 Oct;13(5):396-405. doi: 10.1161/CIRCGEN.120.002929. Epub 2020 Aug 25.

PubMed [citation]

PMID:: 32841044
PMCID:: PMC7676622

Details of each submission

From Ambry Genetics, SCV002625484.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

The p.R1271Q variant (also known as c.3812G>A), located in coding exon 33 of the MYBPC3 gene, results from a G to A substitution at nucleotide position 3812. The arginine at codon 1271 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in a hypertrophic cardiomyopathy (HCM) cohort (Ho CY et al. Circulation, 2018 Oct;138:1387-1398). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#	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: Apr 20, 2024

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