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NM_001927.4(DES):c.1202A>G (p.Glu401Gly) AND Desmin-related myofibrillar myopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Nov 29, 2022
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:
RCV001245293.7

Allele description [Variation Report for NM_001927.4(DES):c.1202A>G (p.Glu401Gly)]

NM_001927.4(DES):c.1202A>G (p.Glu401Gly)

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.1202A>G (p.Glu401Gly)
HGVS:
  • NC_000002.12:g.219421518A>G
  • NG_008043.1:g.8142A>G
  • NM_001382708.1:c.1199A>G
  • NM_001382709.1:c.770A>G
  • NM_001382710.1:c.1133A>G
  • NM_001382711.1:c.1181A>G
  • NM_001382712.1:c.1202A>G
  • NM_001382713.1:c.932A>G
  • NM_001927.4:c.1202A>GMANE SELECT
  • NP_001369637.1:p.Glu400Gly
  • NP_001369638.1:p.Glu257Gly
  • NP_001369639.1:p.Glu378Gly
  • NP_001369640.1:p.Glu394Gly
  • NP_001369641.1:p.Glu401Gly
  • NP_001369642.1:p.Glu311Gly
  • NP_001918.3:p.Glu401Gly
  • LRG_380t1:c.1202A>G
  • LRG_380:g.8142A>G
  • NC_000002.11:g.220286240A>G
  • NM_001927.3:c.1202A>G
Protein change:
E257G
Links:
dbSNP: rs1954444202
NCBI 1000 Genomes Browser:
rs1954444202
Molecular consequence:
  • NM_001382708.1:c.1199A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382709.1:c.770A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382710.1:c.1133A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382711.1:c.1181A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382712.1:c.1202A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382713.1:c.932A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001927.4:c.1202A>G - 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

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001418570Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Nov 29, 2022) 		germlineclinical testing

PubMed (4)
[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

Variable pathogenic potentials of mutations located in the desmin alpha-helical domain.

Goudeau B, Rodrigues-Lima F, Fischer D, Casteras-Simon M, Sambuughin N, de Visser M, Laforet P, Ferrer X, Chapon F, Sjöberg G, Kostareva A, Sejersen T, Dalakas MC, Goldfarb LG, Vicart P.

Hum Mutat. 2006 Sep;27(9):906-13.

PubMed [citation]
PMID:
16865695

Novel Desmin Mutation p.Glu401Asp Impairs Filament Formation, Disrupts Cell Membrane Integrity, and Causes Severe Arrhythmogenic Left Ventricular Cardiomyopathy/Dysplasia.

Bermúdez-Jiménez FJ, Carriel V, Brodehl A, Alaminos M, Campos A, Schirmer I, Milting H, Abril BÁ, Álvarez M, López-Fernández S, García-Giustiniani D, Monserrat L, Tercedor L, Jiménez-Jáimez J.

Circulation. 2018 Apr 10;137(15):1595-1610. doi: 10.1161/CIRCULATIONAHA.117.028719. Epub 2017 Dec 6.

PubMed [citation]
PMID:
29212896
See all PubMed Citations (4)

Details of each submission

From Invitae, SCV001418570.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Glu401 amino acid residue in DES. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16865695, 29212896). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt DES protein function. ClinVar contains an entry for this variant (Variation ID: 969855). This missense change has been observed in individual(s) with dilated cardiomyopathy (PMID: 30847666). This sequence change replaces glutamic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 401 of the DES protein (p.Glu401Gly).

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

Last Updated: Mar 5, 2024