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NM_001927.4(DES):c.1049G>T (p.Arg350Leu) AND Desmin-related myofibrillar myopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jul 26, 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:
RCV001225519.7

Allele description

NM_001927.4(DES):c.1049G>T (p.Arg350Leu)

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.1049G>T (p.Arg350Leu)
HGVS:
  • NC_000002.12:g.219421365G>T
  • NG_008043.1:g.7989G>T
  • NM_001382708.1:c.1046G>T
  • NM_001382709.1:c.736-119G>T
  • NM_001382710.1:c.1024-44G>T
  • NM_001382711.1:c.1028G>T
  • NM_001382712.1:c.1049G>T
  • NM_001382713.1:c.779G>T
  • NM_001927.4:c.1049G>TMANE SELECT
  • NP_001369637.1:p.Arg349Leu
  • NP_001369640.1:p.Arg343Leu
  • NP_001369641.1:p.Arg350Leu
  • NP_001369642.1:p.Arg260Leu
  • NP_001918.3:p.Arg350Leu
  • LRG_380t1:c.1049G>T
  • LRG_380:g.7989G>T
  • NC_000002.11:g.220286087G>T
  • NM_001927.3:c.1049G>T
Protein change:
R260L
Links:
dbSNP: rs57965306
NCBI 1000 Genomes Browser:
rs57965306
Molecular consequence:
  • NM_001382709.1:c.736-119G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001382710.1:c.1024-44G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001382708.1:c.1046G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382711.1:c.1028G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382712.1:c.1049G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382713.1:c.779G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001927.4:c.1049G>T - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001397802Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Jul 26, 2019) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Pathogenic effects of a novel heterozygous R350P desmin mutation on the assembly of desmin intermediate filaments in vivo and in vitro.

Bär H, Fischer D, Goudeau B, Kley RA, Clemen CS, Vicart P, Herrmann H, Vorgerd M, Schröder R.

Hum Mol Genet. 2005 May 15;14(10):1251-60. Epub 2005 Mar 30.

PubMed [citation]
PMID:
15800015

Scapuloperoneal syndrome type Kaeser and a wide phenotypic spectrum of adult-onset, dominant myopathies are associated with the desmin mutation R350P.

Walter MC, Reilich P, Huebner A, Fischer D, Schröder R, Vorgerd M, Kress W, Born C, Schoser BG, Krause KH, Klutzny U, Bulst S, Frey JR, Lochmüller H.

Brain. 2007 Jun;130(Pt 6):1485-96. Epub 2007 Apr 17.

PubMed [citation]
PMID:
17439987
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001397802.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant is not present in population databases (ExAC no frequency). 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 disrupts the p.Arg350 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15800015, 17439987). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with DES-related conditions. This sequence change replaces arginine with leucine at codon 350 of the DES protein (p.Arg350Leu). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and leucine.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 5, 2024