NM_000256.3(MYBPC3):c.1213A>G (p.Met405Val) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 23, 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:: RCV002354345.3

Allele description [Variation Report for NM_000256.3(MYBPC3):c.1213A>G (p.Met405Val)]

NM_000256.3(MYBPC3):c.1213A>G (p.Met405Val)

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.1213A>G (p.Met405Val)

HGVS:

NC_000011.10:g.47343502T>C
NG_007667.1:g.14201A>G
NM_000256.3:c.1213A>GMANE SELECT
NP_000247.2:p.Met405Val
LRG_386t1:c.1213A>G
LRG_386:g.14201A>G
LRG_386p1:p.Met405Val
NC_000011.9:g.47365053T>C

Protein change:

M405V

Links:

dbSNP: rs727503207

NCBI 1000 Genomes Browser:

rs727503207

Molecular consequence:

NM_000256.3:c.1213A>G - 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
SCV002657118	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (May 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25611685, 27532257, 28679633 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002657118

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(May 23, 2023)

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

Results of clinical genetic testing of 2,912 probands with hypertrophic cardiomyopathy: expanded panels offer limited additional sensitivity.

Alfares AA, Kelly MA, McDermott G, Funke BH, Lebo MS, Baxter SB, Shen J, McLaughlin HM, Clark EH, Babb LJ, Cox SW, DePalma SR, Ho CY, Seidman JG, Seidman CE, Rehm HL.

Genet Med. 2015 Nov;17(11):880-8. doi: 10.1038/gim.2014.205. Epub 2015 Jan 22. Erratum in: Genet Med. 2015 Apr;17(4):319. doi: 10.1038/gim.2015.16.

PubMed [citation]

PMID:: 25611685

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

See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV002657118.3

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

Description

The c.1213A>G variant (also known as p.M405V), located in coding exon 13 of the MYBPC3 gene, results from an A to G substitution at nucleotide position 1213. The methionine at codon 405 is replaced by valine, an amino acid with highly similar properties. This variant has been reported in hypertrophic cardiomyopathy (HCM) genetic testing cohorts and individuals reported to have HCM; however, clinical details were limited (Crehalet et al. Cardiogen., 2012; 2:e6; Alfares AA et al. Genet. Med., 2015 Nov;17:880-8; Walsh R et al. Genet. Med., 2017 02;19:192-203). This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site and will result in the creation or strengthening of a novel splice donor site. Limited studies suggest that this variant may have some impact on splicing (Crehalet et al. Cardiogen., 2012; 2:e6; Ito K et al. Proc. Natl. Acad. Sci. U.S.A., 2017 07;114:7689-7694). 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: Sep 29, 2024

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