NM_001927.4(DES):c.735+1G>A AND Myofibrillar myopathy 1

Clinical significance:Likely pathogenic (Last evaluated: May 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000037249.7

Allele description [Variation Report for NM_001927.4(DES):c.735+1G>A]

NM_001927.4(DES):c.735+1G>A

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.735+1G>A
HGVS:
  • NC_000002.12:g.219420347G>A
  • NG_008043.1:g.6971G>A
  • NM_001927.4:c.735+1G>AMANE SELECT
  • LRG_380t1:c.735+1G>A
  • LRG_380:g.6971G>A
  • NC_000002.11:g.220285069G>A
  • NM_001927.3:c.735+1G>A
  • c.735+1G>A
Links:
dbSNP: rs397516698
NCBI 1000 Genomes Browser:
rs397516698
Molecular consequence:
  • NM_001927.4:c.735+1G>A - splice donor variant - [Sequence Ontology: SO:0001575]
Observations:
1

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000060906Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Likely pathogenic
(May 22, 2017)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV001760073Genomics England Pilot Project,Genomics Englandno assertion criteria provided
Likely pathogenicgermlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot provided31not providednot providednot providedclinical testing

Citations

PubMed

Desmin splice variants causing cardiac and skeletal myopathy.

Park KY, Dalakas MC, Goebel HH, Ferrans VJ, Semino-Mora C, Litvak S, Takeda K, Goldfarb LG.

J Med Genet. 2000 Nov;37(11):851-7.

PubMed [citation]
PMID:
11073539
PMCID:
PMC1734475

Desmin myopathy.

Goldfarb LG, Vicart P, Goebel HH, Dalakas MC.

Brain. 2004 Apr;127(Pt 4):723-34. Epub 2004 Jan 14. Review.

PubMed [citation]
PMID:
14724127
See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000060906.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided3not providednot providedclinical testing PubMed (4)

Description

The c.735+1G>A variant in DES has been reported in at least 2 individuals with d esminopathy (Shatunov et al., unpublished data; reviewed by Goldfarb 2004, Gudko va 2013, LMM data), and was absent from large population studies. This variant o ccurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. Ad ditional variants affecting splicing of this exon have been reported in individu als with desminopathy including a different variant at the same position (c.7351 +G>C LMM data: variant occurred de novo) and c.735+3A>G (identified in 6 individ uals with desminopathy and segregated in 9 individuals from 2 families: Park 200 0, Dalakas 2000, Wahni 2012, Greenberg 2012, McDonald 2012, Gudkova 2013, LMM un published data). In summary, although additional studies are required to fully e stablish its clinical significance, the c.735+1G>A variant is likely pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot provided3not provided1not provided

From Genomics England Pilot Project,Genomics England, SCV001760073.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 27, 2021

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