NM_001927.4(DES):c.1034T>C (p.Leu345Pro) AND Myofibrillar myopathy 1

delete

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 1999
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000018319.29

Allele description

NM_001927.4(DES):c.1034T>C (p.Leu345Pro)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.1034T>C (p.Leu345Pro)

HGVS:

NC_000002.12:g.219421350T>C
NG_008043.1:g.7974T>C
NM_001927.4:c.1034T>CMANE SELECT
NP_001918.3:p.Leu345Pro
LRG_380t1:c.1034T>C
LRG_380:g.7974T>C
LRG_380p1:p.Leu345Pro
NC_000002.11:g.220286072T>C
NM_001927.3:c.1034T>C
P17661:p.Leu345Pro

Protein change:

L345P; LEU345PRO

Links:

UniProtKB: P17661#VAR_009189; OMIM: 125660.0006; dbSNP: rs57639980

NCBI 1000 Genomes Browser:

rs57639980

Molecular consequence:

NM_001927.4:c.1034T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Myofibrillar myopathy 1 (MFM1)
Synonyms:: MYOPATHY, MYOFIBRILLAR, DESMIN-RELATED; Desminopathy; Desmin related myopathy (former name); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0011076; MedGen: C1832370; Orphanet: 98909; OMIM: 601419

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
SCV000038598	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 1999)	germline	literature only	PubMed (2) [See all records that cite these PMIDs] 8114783, 10545598

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000038598

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 1999)

germline

literature only

PubMed (2)
[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	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Autosomal dominant distal myopathy with desmin storage: a clinicopathologic and electrophysiologic study of a large kinship.

Horowitz SH, Schmalbruch H.

Muscle Nerve. 1994 Feb;17(2):151-60.

PubMed [citation]

PMID:: 8114783

A missense mutation in the desmin rod domain is associated with autosomal dominant distal myopathy, and exerts a dominant negative effect on filament formation.

Sjöberg G, Saavedra-Matiz CA, Rosen DR, Wijsman EM, Borg K, Horowitz SH, Sejersen T.

Hum Mol Genet. 1999 Nov;8(12):2191-8.

PubMed [citation]

PMID:: 10545598

Details of each submission

From OMIM, SCV000038598.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (2)

Description

In affected members of a large, 6-generation Ashkenazi Jewish family with desmin-related myopathy (MFM1; 601419) reported by Horowitz and Schmalbruch (1994), Sjoberg et al. (1999) identified what they claimed to be the first point mutation in desmin cosegregating with an autosomal dominant form of desmin-related myopathy. The leu345-to-pro mutation (L345P) in this kindred was located in an evolutionarily highly conserved position of the desmin coiled-coil rod domain important for dimer formation. L345P desmin was incapable of forming filamentous networks in transfected HeLa and SW13 cells. Sjoberg et al. (1999) concluded that the L345P mutation causes myopathy by interfering in a dominant-negative manner with the dimerization-polymerization process of intermediate filament assembly.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jul 2, 2022

ClinVar

Relating variation to medicine