NM_017534.6(MYH2):c.4420G>T (p.Glu1474Ter) AND Myopathy, proximal, and ophthalmoplegia

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 27, 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:: RCV003629735.2

Allele description [Variation Report for NM_017534.6(MYH2):c.4420G>T (p.Glu1474Ter)]

NM_017534.6(MYH2):c.4420G>T (p.Glu1474Ter)

Genes:

LOC126862500:BRD4-independent group 4 enhancer GRCh37_chr17:10427829-10429028 [Gene]
MYH2:myosin heavy chain 2 [Gene - OMIM - HGNC]
MYHAS:myosin heavy chain gene cluster antisense RNA [Gene - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

17p13.1

Genomic location:

Preferred name:

NM_017534.6(MYH2):c.4420G>T (p.Glu1474Ter)

HGVS:

NC_000017.11:g.10525568C>A
NG_013014.1:g.29133G>T
NG_086998.1:g.1157C>A
NM_001100112.2:c.4420G>T
NM_017534.6:c.4420G>TMANE SELECT
NP_001093582.1:p.Glu1474Ter
NP_060004.3:p.Glu1474Ter
NC_000017.10:g.10428885C>A

Protein change:

E1474*

Molecular consequence:

NM_001100112.2:c.4420G>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017534.6:c.4420G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Myopathy, proximal, and ophthalmoplegia (CMYO6)
Synonyms:: Inclusion body myopathy 3; Myopathy with congenital joint contractures, ophthalmoplegia, and rimmed vacuoles; Inclusion body myopathy autosomal dominant; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011577; MedGen: C1854106; Orphanet: 363677; Orphanet: 79091; OMIM: 605637

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004532031	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 27, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 20418530, 23388406, 24193343, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004532031

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 27, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Human disease caused by loss of fast IIa myosin heavy chain due to recessive MYH2 mutations.

Tajsharghi H, Hilton-Jones D, Raheem O, Saukkonen AM, Oldfors A, Udd B.

Brain. 2010 May;133(Pt 5):1451-9. doi: 10.1093/brain/awq083.

PubMed [citation]

PMID:: 20418530

MYH2 mutation in recessive myopathy with external ophthalmoplegia linked to chromosome 17p13.1-p12.

Lossos A, Oldfors A, Fellig Y, Meiner V, Argov Z, Tajsharghi H.

Brain. 2013 Jul;136(Pt 7):e238. doi: 10.1093/brain/aws365. Epub 2013 Feb 6. No abstract available.

PubMed [citation]

PMID:: 23388406

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004532031.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change creates a premature translational stop signal (p.Glu1474*) in the MYH2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in MYH2 are known to be pathogenic (PMID: 20418530, 23388406, 24193343). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with MYH2-related conditions. For these reasons, this variant has been 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

Last Updated: Sep 29, 2024

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