NM_000256.3(MYBPC3):c.3065G>A (p.Arg1022His) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 29, 2019
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:: RCV000035554.7

Allele description [Variation Report for NM_000256.3(MYBPC3):c.3065G>A (p.Arg1022His)]

NM_000256.3(MYBPC3):c.3065G>A (p.Arg1022His)

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.3065G>A (p.Arg1022His)

HGVS:

NC_000011.10:g.47333682C>T
NG_007667.1:g.24021G>A
NM_000256.3:c.3065G>AMANE SELECT
NP_000247.2:p.Arg1022His
LRG_386t1:c.3065G>A
LRG_386:g.24021G>A
LRG_386p1:p.Arg1022His
NC_000011.9:g.47355233C>T
c.3065G>A

Protein change:

R1022H

Links:

dbSNP: rs397516000

NCBI 1000 Genomes Browser:

rs397516000

Molecular consequence:

NM_000256.3:c.3065G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000059204	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Aug 29, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 27532257, 28790153, 24033266

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000059204

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Aug 29, 2019)

germline

clinical testing

PubMed (3)
[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	1	1	not provided	not provided	not provided	clinical testing

Citations

PubMed

Reassessment of Mendelian gene pathogenicity using 7,855 cardiomyopathy cases and 60,706 reference samples.

Walsh R, Thomson KL, Ware JS, Funke BH, Woodley J, McGuire KJ, Mazzarotto F, Blair E, Seller A, Taylor JC, Minikel EV, Exome Aggregation Consortium, MacArthur DG, Farrall M, Cook SA, Watkins H.

Genet Med. 2017 Feb;19(2):192-203. doi: 10.1038/gim.2016.90. Epub 2016 Aug 17.

PubMed [citation]

PMID:: 27532257
PMCID:: PMC5116235

Multiple Gene Variants in Hypertrophic Cardiomyopathy in the Era of Next-Generation Sequencing.

Burns C, Bagnall RD, Lam L, Semsarian C, Ingles J.

Circ Cardiovasc Genet. 2017 Aug;10(4). doi:pii: e001666. 10.1161/CIRCGENETICS.116.001666.

PubMed [citation]

PMID:: 28790153

See all PubMed Citations (3)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000059204.6

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

Description

Variant classified as Uncertain Significance - Favor Pathogenic. The p.Arg1022His variant in MYBPC3 has been identified in 2 individuals with HCM, one of whom was homozygous (Burns 2017, LMM data). It was also identified in 2/278058 chromosomes by gnomAD (https://gnomad.broadinstitute.org) and has been reported in ClinVar (Variation ID#42681). Computational tools suggest that this variant may impact protein function; however, this information is not predictive enough to determine pathogenicity. In addition, two other variants involving this codon, p.Arg1022Cys and p.Arg1022Pro, have been identified in individuals with HCM, suggesting that changes at this position may not be tolerated. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM5_Supporting, PP3.

#	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		1	not provided	1	not provided

Last Updated: Oct 8, 2024

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