NM_000257.4(MYH7):c.3346G>T (p.Glu1116Ter) AND Cardiomyopathy

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 15, 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:: RCV004018058.1

Allele description [Variation Report for NM_000257.4(MYH7):c.3346G>T (p.Glu1116Ter)]

NM_000257.4(MYH7):c.3346G>T (p.Glu1116Ter)

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.3346G>T (p.Glu1116Ter)

HGVS:

NC_000014.9:g.23420225C>A
NG_007884.1:g.20437G>T
NM_000257.4:c.3346G>TMANE SELECT
NM_001407004.1:c.3346G>T
NP_000248.2:p.Glu1116Ter
NP_000248.2:p.Glu1116Ter
NP_001393933.1:p.Glu1116Ter
LRG_384t1:c.3346G>T
LRG_384:g.20437G>T
LRG_384p1:p.Glu1116Ter
NC_000014.8:g.23889434C>A
NM_000257.2:c.3346G>T

Protein change:

E1116*

Molecular consequence:

NM_000257.4:c.3346G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001407004.1:c.3346G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Cardiomyopathy (CMYO)
Synonyms:: Cardiomyopathies
Identifiers:: MONDO: MONDO:0004994; MedGen: C0878544; Human Phenotype Ontology: HP:0001638

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004847597	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely Pathogenic (Feb 15, 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

SCV004847597

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely Pathogenic
(Feb 15, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV004847597.1

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

Description

The p.Glu1116X variant in MYH7 has not been previously reported in individuals with hypertrophic cardiomyopathy (HCM) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1116, which is predicted to lead to a truncated or absent protein. Although heterozygous loss-of-function (LOF) variants in MYH7, such as this variant, are not believed to be pathogenic for dominant forms of cardiomyopathy, there is evidence that can they lead to severe and early onset disease when present in trans with a second MYH7 variant (LMM data). In summary, although additional studies are required to fully establish its clinical significance, the p.Glu1116X variant is likely pathogenic. ACMG/AMP Criteria applied: PVS1, PM2.

#	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: May 7, 2024

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