NM_001927.4(DES):c.738G>C (p.Glu246Asp) AND Desmin-related myofibrillar myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 23, 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:: RCV001036926.15

Allele description [Variation Report for NM_001927.4(DES):c.738G>C (p.Glu246Asp)]

NM_001927.4(DES):c.738G>C (p.Glu246Asp)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.738G>C (p.Glu246Asp)

HGVS:

NC_000002.12:g.219420497G>C
NG_008043.1:g.7121G>C
NM_001927.4:c.738G>CMANE SELECT
NP_001918.3:p.Glu246Asp
LRG_380t1:c.738G>C
LRG_380:g.7121G>C
NC_000002.11:g.220285219G>C
NM_001927.3:c.738G>C

Protein change:

E246D

Links:

dbSNP: rs1954417703

NCBI 1000 Genomes Browser:

rs1954417703

Molecular consequence:

NM_001927.4:c.738G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Desmin-related myofibrillar myopathy (MFM1)
Synonyms:: Desminopathy; Desmin related myopathy (former name); Desmin storage myopathy (former name); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011076; MedGen: C1832370; Orphanet: 363543; Orphanet: 98909; OMIM: 601419

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001200314	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 23, 2019)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19005210, 16449718, 14724127, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001200314

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 23, 2019)

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

A myopathy-linked desmin mutation perturbs striated muscle actin filament architecture.

Conover GM, Henderson SN, Gregorio CC.

Mol Biol Cell. 2009 Feb;20(3):834-45. doi: 10.1091/mbc.E08-07-0753. Epub 2008 Nov 12.

PubMed [citation]

PMID:: 19005210
PMCID:: PMC2633376

Images in cardiovascular medicine. Giant right atrium in the setting of desmin-related restrictive cardiomyopathy.

Hager S, Mahrholdt H, Goldfarb LG, Goebel HH, Sechtem U.

Circulation. 2006 Jan 31;113(4):e53-5. No abstract available.

PubMed [citation]

PMID:: 16449718

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001200314.5

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. This variant has been reported to affect DES protein function (PMID: 19005210). This variant has been observed in individual(s) with DES-related conditions (PMID: 16449718, 14724127). This variant is also known as Glu245Asp in the literature. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamic acid with aspartic acid at codon 246 of the DES protein (p.Glu246Asp). The glutamic acid residue is highly conserved and there is a small physicochemical difference between glutamic acid and aspartic acid.

#	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: Nov 3, 2024

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