NM_017534.6(MYH2):c.1358A>G (p.Lys453Arg) AND Myopathy, proximal, and ophthalmoplegia

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 7, 2017
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:: RCV000544916.1

Allele description [Variation Report for NM_017534.6(MYH2):c.1358A>G (p.Lys453Arg)]

NM_017534.6(MYH2):c.1358A>G (p.Lys453Arg)

Genes:

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.1358A>G (p.Lys453Arg)

HGVS:

NC_000017.11:g.10539263T>C
NG_013014.1:g.15438A>G
NM_001100112.2:c.1358A>G
NM_017534.6:c.1358A>GMANE SELECT
NP_001093582.1:p.Lys453Arg
NP_060004.3:p.Lys453Arg
NC_000017.10:g.10442580T>C
NM_017534.5:c.1358A>G

Protein change:

K453R

Links:

dbSNP: rs1555571482

NCBI 1000 Genomes Browser:

rs1555571482

Molecular consequence:

NM_001100112.2:c.1358A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_017534.6:c.1358A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myopathy, proximal, and ophthalmoplegia (CMYP6)
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

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000641369	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 7, 2017)	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

SCV000641369

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 7, 2017)

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV000641369.1

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

Description

This sequence change replaces lysine with arginine at codon 453 of the MYH2 protein (p.Lys453Arg). The lysine residue is highly conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a MYH2-related disease. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C25"). In summary, this variant is a novel missense change with uncertain impact on protein function. It has been classified as a Variant of Uncertain Significance.

#	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: Aug 5, 2023

ClinVar

Relating variation to medicine