NM_000257.4(MYH7):c.1106G>A (p.Arg369Gln) AND Cardiovascular phenotype

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Feb 11, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000587847.10

Allele description [Variation Report for NM_000257.4(MYH7):c.1106G>A (p.Arg369Gln)]

NM_000257.4(MYH7):c.1106G>A (p.Arg369Gln)

Gene:

MYH7:myosin heavy chain 7 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

14q11.2

Genomic location:

Preferred name:

NM_000257.4(MYH7):c.1106G>A (p.Arg369Gln)

Other names:

p.R369Q:CGG>CAG; NM_000257.3(MYH7):c.1106G>A; NM_000257.4(MYH7):c.1106G>A

HGVS:

NC_000014.9:g.23429807C>T
NG_007884.1:g.10855G>A
NM_000257.4:c.1106G>AMANE SELECT
NP_000248.2:p.Arg369Gln
LRG_384t1:c.1106G>A
LRG_384:g.10855G>A
NC_000014.8:g.23899016C>T
NM_000257.2:c.1106G>A
NM_000257.3:c.1106G>A
c.1106G>A

Protein change:

R369Q

Links:

dbSNP: rs397516089

NCBI 1000 Genomes Browser:

rs397516089

Molecular consequence:

NM_000257.4:c.1106G>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
SCV000696337	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Aug 15, 2017)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 18519860, 22464770, 24691700, 24503780, 27532257, 20530761 LabCorp Variant Classification Summary - May 2015.docx, Citation Link,
SCV000735357	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (Feb 11, 2021)	germline	clinical testing	PubMed (10) [See all records that cite these PMIDs] 20031619, 20530761, 22464770, 24691700, 27532257, 29253866, 29300372, 29892087, 30371277, 32458740 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000696337

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Aug 15, 2017)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV000735357

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(Feb 11, 2021)

germline

clinical testing

PubMed (10)
[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

Sarcomere mutations in cardiomyopathy, noncompaction, and the developing heart.

Dellefave L, McNally EM.

Circulation. 2008 Jun 3;117(22):2847-9. doi: 10.1161/CIRCULATIONAHA.108.781518. Review. No abstract available.

PubMed [citation]

PMID:: 18519860

The landscape of genetic variation in dilated cardiomyopathy as surveyed by clinical DNA sequencing.

Pugh TJ, Kelly MA, Gowrisankar S, Hynes E, Seidman MA, Baxter SM, Bowser M, Harrison B, Aaron D, Mahanta LM, Lakdawala NK, McDermott G, White ET, Rehm HL, Lebo M, Funke BH.

Genet Med. 2014 Aug;16(8):601-8. doi: 10.1038/gim.2013.204. Epub 2014 Feb 6.

PubMed [citation]

PMID:: 24503780

See all PubMed Citations (12)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696337.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

Variant summary: The MYH7 c.1106G>A (p.Arg369Gln) variant causes a missense change involving the alteration of a conserved nucleotide located in the P-loop containing nucleoside triphosphate hydrolase domain (IPR027417) (InterPro). 3/5 in silico tools predict a damaging outcome for this variant. This variant was not found in the large control database ExAC and a published study (Lakdawala_TNNT2_J Cardiac Failure_2012) in 122186 control chromosomes. This variant was found in multiple DCM pediatric patients, including de novo occurrences (Walsh_2017, Tian_2015, Lakdawala_2012, Pugh_2014). This variant was also associated with Left ventricular non-compaction (LVNC) in addition to DCM (Dellefave_2009, Hoedemaekers_2010, Tian_2015). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.

#	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

From Ambry Genetics, SCV000735357.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (10)

Description

The p.R369Q pathogenic mutation (also known as c.1106G>A), located in coding exon 10 of the MYH7 gene, results from a G to A substitution at nucleotide position 1106. The arginine at codon 369 is replaced by glutamine, an amino acid with highly similar properties, and is located in the head domain. This alteration has been detected in individuals reported to have left ventricular non-compaction and individuals reported with dilated cardiomyopathy; the alteration has also been reported as occurring in an apparent de novo state in affected individuals and also has shown segregation with disease in families (Dellefave LM et al. Circ Cardiovasc Genet. 2009;2(5):442-9; Lakdawala NK et al. J Card Fail. 2012;18(4):296-303; Tian T et al. Heart Vessels. 2015;30(2):258-64; Walsh R et al. Genet. Med., 2017 Feb;19:192-203; Horvat C et al. Genet Med. 2019 01;21(1):133-143). Based on the supporting evidence, 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: Nov 24, 2024

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