U.S. flag

An official website of the United States government

NM_001927.4(DES):c.2T>C (p.Met1Thr) AND Desmin-related myofibrillar myopathy

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jun 29, 2020
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:
RCV001377481.6

Allele description [Variation Report for NM_001927.4(DES):c.2T>C (p.Met1Thr)]

NM_001927.4(DES):c.2T>C (p.Met1Thr)

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.2T>C (p.Met1Thr)
HGVS:
  • NC_000002.12:g.219418464T>C
  • NG_008043.1:g.5088T>C
  • NG_046330.1:g.18856T>C
  • NM_001382708.1:c.2T>C
  • NM_001382709.1:c.2T>C
  • NM_001382710.1:c.2T>C
  • NM_001382711.1:c.2T>C
  • NM_001382712.1:c.2T>C
  • NM_001382713.1:c.2T>C
  • NM_001927.4:c.2T>CMANE SELECT
  • NP_001369637.1:p.Met1Thr
  • NP_001369638.1:p.Met1Thr
  • NP_001369639.1:p.Met1Thr
  • NP_001369640.1:p.Met1Thr
  • NP_001369641.1:p.Met1Thr
  • NP_001369642.1:p.Met1Thr
  • NP_001918.3:p.Met1Thr
  • LRG_380:g.5088T>C
  • NC_000002.11:g.220283186T>C
Protein change:
M1T
Links:
dbSNP: rs2125165615
NCBI 1000 Genomes Browser:
rs2125165615
Molecular consequence:
  • NM_001382708.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382709.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382710.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382711.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382712.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382713.1:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001927.4:c.2T>C - initiator_codon_variant - [Sequence Ontology: SO:0001582]
  • NM_001382708.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382709.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382710.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382711.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382712.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382713.1:c.2T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001927.4:c.2T>C - 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

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001574822Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Likely pathogenic
(Jun 29, 2020) 		germlineclinical testing

PubMed (2)
[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

A series of Chinese patients with desminopathy associated with six novel and one reported mutations in the desmin gene.

Hong D, Wang Z, Zhang W, Xi J, Lu J, Luan X, Yuan Y.

Neuropathol Appl Neurobiol. 2011 Apr;37(3):257-70. doi: 10.1111/j.1365-2990.2010.01112.x.

PubMed [citation]
PMID:
20696008

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001574822.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

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 initiator methionine in DES. If translation initiates from the next-in-frame methionine, the DES protein would no longer include the region containing p.Ser12 amino acid residue. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 20696008, Invitae). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. This variant has not been reported in the literature in individuals with DES-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects the initiator methionine of the DES mRNA. The next in-frame methionine is located at codon 263.

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

Last Updated: Mar 5, 2024