NM_001927.4(DES):c.769C>T (p.Gln257Ter) AND Desmin-related myofibrillar myopathy

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 19, 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:: RCV003792546.2

Allele description [Variation Report for NM_001927.4(DES):c.769C>T (p.Gln257Ter)]

NM_001927.4(DES):c.769C>T (p.Gln257Ter)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.769C>T (p.Gln257Ter)

HGVS:

NC_000002.12:g.219420528C>T
NG_008043.1:g.7152C>T
NM_001382708.1:c.766C>T
NM_001382709.1:c.735+182C>T
NM_001382710.1:c.769C>T
NM_001382711.1:c.769C>T
NM_001382712.1:c.769C>T
NM_001382713.1:c.499C>T
NM_001927.4:c.769C>TMANE SELECT
NP_001369637.1:p.Gln256Ter
NP_001369639.1:p.Gln257Ter
NP_001369640.1:p.Gln257Ter
NP_001369641.1:p.Gln257Ter
NP_001369642.1:p.Gln167Ter
NP_001918.3:p.Gln257Ter
NP_001918.3:p.Gln257Ter
LRG_380t1:c.769C>T
LRG_380:g.7152C>T
LRG_380p1:p.Gln257Ter
NC_000002.11:g.220285250C>T
NM_001927.3:c.769C>T

Protein change:

Q167*

Molecular consequence:

NM_001382709.1:c.735+182C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001382708.1:c.766C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001382710.1:c.769C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001382711.1:c.769C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001382712.1:c.769C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001382713.1:c.499C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001927.4:c.769C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004588743	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 19, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23575897, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004588743

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 19, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Recessive desmin-null muscular dystrophy with central nuclei and mitochondrial abnormalities.

Henderson M, De Waele L, Hudson J, Eagle M, Sewry C, Marsh J, Charlton R, He L, Blakely EL, Horrocks I, Stewart W, Taylor RW, Longman C, Bushby K, Barresi R.

Acta Neuropathol. 2013 Jun;125(6):917-9. doi: 10.1007/s00401-013-1113-x. Epub 2013 Apr 11. No abstract available.

PubMed [citation]

PMID:: 23575897

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004588743.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals affected with DES-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln257*) in the DES gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DES are known to be pathogenic (PMID: 23575897).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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