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GRCh38/hg38 2q35(chr2:219420345-219431647)x1 AND Desmin-related myofibrillar myopathy

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Aug 24, 2023
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:
RCV003327659.3

Allele description [Variation Report for GRCh38/hg38 2q35(chr2:219420345-219431647)x1]

GRCh38/hg38 2q35(chr2:219420345-219431647)x1

Genes:
LOC110121267:VISTA enhancer hs2169 [Gene]
DES:desmin [Gene - OMIM - HGNC]
Variant type:
copy number loss
Cytogenetic location:
2q35
Genomic location:
Chr2: 219420345 - 219431647 (on Assembly GRCh38)
Preferred name:
GRCh38/hg38 2q35(chr2:219420345-219431647)x1
HGVS:

    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
    SCV004034193Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
    criteria provided, single submitter

    (ACMG/ClinGen CNV Guidelines, 2019)    		Pathogenic
    (Aug 24, 2023)     		unknownresearch

    PubMed (2)
    [See all records that cite these PMIDs]

    Help

    Summary from all submissions

    EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
    not providedunknownyesnot providednot providednot providednot providednot providedresearch

    Citations

    PubMed

    Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen).

    Riggs ER, Andersen EF, Cherry AM, Kantarci S, Kearney H, Patel A, Raca G, Ritter DI, South ST, Thorland EC, Pineda-Alvarez D, Aradhya S, Martin CL.

    Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6. Erratum in: Genet Med. 2021 Nov;23(11):2230. doi: 10.1038/s41436-021-01150-9.

    PubMed [citation]
    PMID:
    31690835
    PMCID:
    PMC7313390

    Sequential targeted exome sequencing of 1001 patients affected by unexplained limb-girdle weakness.

    Töpf A, Johnson K, Bates A, Phillips L, Chao KR, England EM, Laricchia KM, Mullen T, Valkanas E, Xu L, Bertoli M, Blain A, Casasús AB, Duff J, Mroczek M, Specht S, Lek M, Ensini M, MacArthur DG; MYO-SEQ consortium., Straub V.

    Genet Med. 2020 Sep;22(9):1478-1488. doi: 10.1038/s41436-020-0840-3. Epub 2020 Jun 11.

    PubMed [citation]
    PMID:
    32528171
    PMCID:
    PMC7462745

    Details of each submission

    From Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard, SCV004034193.1

    #EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
    1not providednot providednot providednot providedresearch PubMed (2)

    Description

    A heterozygous deletion of exons 4-9 in DES (NM_001927.4) was identified by exome sequencing and confirmed by genome sequencing in one individual with myofibrillar myopathy ([GRCh 38] chr2:219420345_219431647x1)(PMID: 32528171). Inheritance information is unavailable. The patient phenotype is nonspecific, but is consistent with cases described in the literature and/or published databases with overlapping variants. There is partial overlap with the 3’ end and additional exons (NMD is expected to occur) of the DES gene. This gene has a definitive gene-disease relationship to dilated cardiomyopathy and myofibrillar myopathy and the reported mechanism is loss-of-function (https://search.thegencc.org/genes). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant myofibrillar myopathy. The ACMG/ClinGen evidence codes and points used in this curation are as follows: 1: 0 points, 2: 0.90 points, 3: 0 points, 4-5: 0.1 points; Total: 1.00 points; Riggs 2020 (PMID: 31690835).

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

    Last Updated: Jun 23, 2024