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NM_001927.4(DES):c.575C>T (p.Ala192Val) AND Desmin-related myofibrillar myopathy

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Dec 4, 2021
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:
RCV001928849.3

Allele description

NM_001927.4(DES):c.575C>T (p.Ala192Val)

Gene:
DES:desmin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q35
Genomic location:
Preferred name:
NM_001927.4(DES):c.575C>T (p.Ala192Val)
HGVS:
  • NC_000002.12:g.219419037C>T
  • NG_008043.1:g.5661C>T
  • NM_001382708.1:c.575C>T
  • NM_001382709.1:c.575C>T
  • NM_001382710.1:c.575C>T
  • NM_001382711.1:c.575C>T
  • NM_001382712.1:c.575C>T
  • NM_001382713.1:c.495+80C>T
  • NM_001927.4:c.575C>TMANE SELECT
  • NP_001369637.1:p.Ala192Val
  • NP_001369638.1:p.Ala192Val
  • NP_001369639.1:p.Ala192Val
  • NP_001369640.1:p.Ala192Val
  • NP_001369641.1:p.Ala192Val
  • NP_001918.3:p.Ala192Val
  • LRG_380:g.5661C>T
  • NC_000002.11:g.220283759C>T
Protein change:
A192V
Links:
dbSNP: rs889191100
NCBI 1000 Genomes Browser:
rs889191100
Molecular consequence:
  • NM_001382713.1:c.495+80C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001382708.1:c.575C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382709.1:c.575C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382710.1:c.575C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382711.1:c.575C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382712.1:c.575C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001927.4:c.575C>T - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002204241Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Dec 4, 2021) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

Citations

PubMed

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 Invitae, SCV002204241.3

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

Description

Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 192 of the DES protein (p.Ala192Val). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Feb 28, 2024