NM_001927.4(DES):c.1325C>T (p.Thr442Ile) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Dec 10, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000811753.1

Allele description [Variation Report for NM_001927.4(DES):c.1325C>T (p.Thr442Ile)]

NM_001927.4(DES):c.1325C>T (p.Thr442Ile)

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.1325C>T (p.Thr442Ile)
HGVS:
  • NC_000002.12:g.219425699C>T
  • NG_008043.1:g.12323C>T
  • NM_001927.4:c.1325C>TMANE SELECT
  • NP_001918.3:p.Thr442Ile
  • LRG_380t1:c.1325C>T
  • LRG_380:g.12323C>T
  • LRG_380p1:p.Thr442Ile
  • NC_000002.11:g.220290421C>T
  • NM_001927.3:c.1325C>T
  • P17661:p.Thr442Ile
Protein change:
T442I; THR442ILE
Links:
UniProtKB: P17661#VAR_042459; OMIM: 125660.0015; dbSNP: rs121913005
NCBI 1000 Genomes Browser:
rs121913005
Molecular consequence:
  • NM_001927.4:c.1325C>T - 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
Name:
Muscular dystrophy, limb-girdle, type 2R (LGMD2R)
Synonyms:
Autosomal recessive limb-girdle muscular dystrophy type 2R
Identifiers:
MONDO: MONDO:0014129; MedGen: C3809137; Orphanet: 363543

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000952036Invitaecriteria provided, single submitter
Pathogenic
(Dec 10, 2018)
germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D.

van Spaendonck-Zwarts KY, van der Kooi AJ, van den Berg MP, Ippel EF, Boven LG, Yee WC, van den Wijngaard A, Brusse E, Hoogendijk JE, Doevendans PA, de Visser M, Jongbloed JD, van Tintelen JP.

Neth Heart J. 2012 May;20(5):219-28. doi: 10.1007/s12471-011-0233-y.

PubMed [citation]
PMID:
22215463
PMCID:
PMC3346870

Desmin mutations in the terminal consensus motif prevent synemin-desmin heteropolymer filament assembly.

Chourbagi O, Bruston F, Carinci M, Xue Z, Vicart P, Paulin D, Agbulut O.

Exp Cell Res. 2011 Apr 1;317(6):886-97. doi: 10.1016/j.yexcr.2011.01.013. Epub 2011 Jan 22.

PubMed [citation]
PMID:
21262226
See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000952036.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

This sequence change replaces threonine with isoleucine at codon 442 of the DES protein (p.Thr442Ile). The threonine residue is moderately conserved and there is a moderate physicochemical difference between threonine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with autosomal dominant cardiac and skeletal myopathy in families (PMID: 17221859, 22153487) and has been reported in several individuals affected with autosomal dominant myofibrillar myopathy and desmin-related myopathy (PMID:18653338, 22215463). ClinVar contains an entry for this variant (Variation ID: 16834). Experimental studies have shown that this missense change affects desmin assembly and aggregate formation (PMID: 17221859, 21262226). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Oct 7, 2021

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