NM_000257.4(MYH7):c.4075C>T (p.Arg1359Cys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jul 1, 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:: RCV000201890.2

Allele description [Variation Report for NM_000257.4(MYH7):c.4075C>T (p.Arg1359Cys)]

NM_000257.4(MYH7):c.4075C>T (p.Arg1359Cys)

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.4075C>T (p.Arg1359Cys)

Other names:

p.R1359C:CGC>TGC; NM_000257.3(MYH7):c.4075C>T(p.Arg1359Cys)

HGVS:

NC_000014.9:g.23418304G>A
NG_007884.1:g.22358C>T
NM_000257.4:c.4075C>TMANE SELECT
NP_000248.2:p.Arg1359Cys
LRG_384t1:c.4075C>T
LRG_384:g.22358C>T
NC_000014.8:g.23887513G>A
NM_000257.2:c.4075C>T
NM_000257.3:c.4075C>T
P12883:p.Arg1359Cys

Protein change:

R1359C

Links:

UniProtKB: P12883#VAR_073883; dbSNP: rs45451303

NCBI 1000 Genomes Browser:

rs45451303

Molecular consequence:

NM_000257.4:c.4075C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Primary dilated cardiomyopathy (DCM)
Synonyms:: Dilated Cardiomyopathy
Identifiers:: EFO: EFO_0000407; MONDO: MONDO:0005021; MeSH: D002311; MedGen: C0007193; Human Phenotype Ontology: HP:0001644

Name:: Hypertrophic cardiomyopathy
Synonyms:: HYPERTROPHIC MYOCARDIOPATHY
Identifiers:: MONDO: MONDO:0005045; MeSH: D002312; MedGen: C0007194; Human Phenotype Ontology: HP:0001639

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000256637	Agnes Ginges Centre for Molecular Cardiology, Centenary Institute	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Jul 1, 2019)	germline	research	PubMed (5) [See all records that cite these PMIDs] 19412328, 18506004, 20965760, 29447731, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000256637

Agnes Ginges Centre for Molecular Cardiology, Centenary Institute

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Jul 1, 2019)

germline

research

PubMed (5)
[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	yes	not provided	not provided	not provided	not provided	not provided	research

Citations

PubMed

Coding sequence mutations identified in MYH7, TNNT2, SCN5A, CSRP3, LBD3, and TCAP from 313 patients with familial or idiopathic dilated cardiomyopathy.

Hershberger RE, Parks SB, Kushner JD, Li D, Ludwigsen S, Jakobs P, Nauman D, Burgess D, Partain J, Litt M.

Clin Transl Sci. 2008 May;1(1):21-6. doi: 10.1111/j.1752-8062.2008.00017.x.

PubMed [citation]

PMID:: 19412328
PMCID:: PMC2633921

Mutations in sarcomere protein genes in left ventricular noncompaction.

Klaassen S, Probst S, Oechslin E, Gerull B, Krings G, Schuler P, Greutmann M, Hürlimann D, Yegitbasi M, Pons L, Gramlich M, Drenckhahn JD, Heuser A, Berger F, Jenni R, Thierfelder L.

Circulation. 2008 Jun 3;117(22):2893-901. doi: 10.1161/CIRCULATIONAHA.107.746164. Epub 2008 May 27.

PubMed [citation]

PMID:: 18506004

See all PubMed Citations (5)

Details of each submission

From Agnes Ginges Centre for Molecular Cardiology, Centenary Institute, SCV000256637.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	research	PubMed (5)

Description

MYH7 Arg1359Cys variant is present in the Genome Aggregation Database (http://gnomad.broadinstitute.org/) at an allele frequency of 0.000081. This variant has been reported in cases with left ventricular noncompaction (Waning et al., 2018; Chang et al., 2011; Klaassen et al., 2008) and DCM (Hershberger et al. 2008). We have identified this variant in a HCM proband diagnosed late in life with no family history of disease and no other variants to explain her phenotype (Ingles J et al., 2017) and second proband with DCM. In silico tools (SIFT, PolyPhen-2, MutationTaster) are in agreement and supportive of deleterious role. Based on this evidence we classify MYH7 Arg1359Cys as a variant of 'uncertain significance'.

#	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: Sep 29, 2024

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