NM_000257.4(MYH7):c.2155C>T (p.Arg719Trp) AND Hypertrophic cardiomyopathy 1

Germline classification:: Pathogenic (3 submissions)
Last evaluated:: Apr 16, 2019
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:: RCV000015160.30

Allele description [Variation Report for NM_000257.4(MYH7):c.2155C>T (p.Arg719Trp)]

NM_000257.4(MYH7):c.2155C>T (p.Arg719Trp)

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.2155C>T (p.Arg719Trp)

Other names:

p.R719W:CGG>TGG; NM_000257.3(MYH7):c.2155C>T

HGVS:

NC_000014.9:g.23425971G>A
NG_007884.1:g.14691C>T
NM_000257.4:c.2155C>TMANE SELECT
NP_000248.2:p.Arg719Trp
LRG_384t1:c.2155C>T
LRG_384:g.14691C>T
NC_000014.8:g.23895180G>A
NM_000257.2:c.2155C>T
NM_000257.3:c.2155C>T
P12883:p.Arg719Trp
c.2155C>T

Protein change:

R719W; ARG719TRP

Links:

UniProtKB: P12883#VAR_004584; OMIM: 160760.0017; dbSNP: rs121913637

NCBI 1000 Genomes Browser:

rs121913637

Molecular consequence:

NM_000257.4:c.2155C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Hypertrophic cardiomyopathy 1
Synonyms:: Familial hypertrophic cardiomyopathy 1; MYH7-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0008647; MedGen: C3495498; OMIM: 192600

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MULTISPECIES: 30S ribosomal protein S18 [Cyanophyceae]
MULTISPECIES: 30S ribosomal protein S18 [Cyanophyceae]
gi|1909762006|ref|WP_190643059.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000035417	OMIM	no assertion criteria provided	Pathogenic (Mar 1, 1998)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8282798, 9544842
SCV000679782	Phosphorus, Inc.	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Aug 1, 2017)	germline	clinical testing	PubMed (28) [See all records that cite these PMIDs] 7874131, 8282798, 9001794, 9154300, 9544842, 9822100, 10882745, 10957787, 11904418, 12084606, 12707239, 15000344, 16504640, 18414213, 19645038, 19651039, 20378854, 21310275, 21769673, 22429680, 23816408, 24033266, 24888384, 25611685, 27082122, 27247418, 27532257, 25741868
SCV001433414	Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Apr 16, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000035417

OMIM

no assertion criteria provided

Pathogenic
(Mar 1, 1998)

germline

literature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000679782

Phosphorus, Inc.

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Aug 1, 2017)

germline

clinical testing

PubMed (28)
[See all records that cite these PMIDs]

SCV001433414

Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Apr 16, 2019)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Isolation of a de novo mutant myocardial beta MHC protein in a pedigree with hypertrophic cardiomyopathy.

Greve G, Bachinski L, Friedman DL, Czernuzewicz G, Anan R, Towbin J, Seidman CE, Roberts R.

Hum Mol Genet. 1994 Nov;3(11):2073-5. No abstract available.

PubMed [citation]

PMID:: 7874131

Prognostic implications of novel beta cardiac myosin heavy chain gene mutations that cause familial hypertrophic cardiomyopathy.

Anan R, Greve G, Thierfelder L, Watkins H, McKenna WJ, Solomon S, Vecchio C, Shono H, Nakao S, Tanaka H, et al.

J Clin Invest. 1994 Jan;93(1):280-5.

PubMed [citation]

PMID:: 8282798
PMCID:: PMC293763

See all PubMed Citations (28)

Details of each submission

From OMIM, SCV000035417.2

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

Description

In 4 unrelated families with hypertrophic cardiomyopathy (CMH1; 192600) with a high incidence of premature death and an average life expectancy in affected individuals of 38 years, Anan et al. (1994) found an R719W mutation in exon 19 changing the charge of the amino acid by -1. The difference in survival of individuals bearing the R719W mutation as compared with those with the F513C mutation (160760.0016) was demonstrated by Kaplan-Meier product-limit curves (their Figure 4).

In a 6.5-year-old boy with a severe form of hypertrophic cardiomyopathy, Jeschke et al. (1998) identified 2 missense mutations: one was the R719W mutation and the other was an M349T mutation (160760.0020), which was inherited through the maternal grandmother. Six family members who were carriers of the M349T mutation were clinically unaffected. The authors hypothesized that compound heterozygosity for the R719W and M349T mutations resulted in the particularly severe phenotype of early onset.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Phosphorus, Inc., SCV000679782.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (28)

#	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	not provided	not provided

From Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease, Montreal Heart Institute, SCV001433414.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Nov 3, 2024

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