NM_001927.4(DES):c.986A>G (p.Gln329Arg) AND Desmin-related myofibrillar myopathy

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 31, 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:: RCV003809105.1

Allele description

NM_001927.4(DES):c.986A>G (p.Gln329Arg)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.986A>G (p.Gln329Arg)

HGVS:

NC_000002.12:g.219420916A>G
NG_008043.1:g.7540A>G
NM_001382708.1:c.983A>G
NM_001382709.1:c.736-568A>G
NM_001382710.1:c.986A>G
NM_001382711.1:c.986A>G
NM_001382712.1:c.986A>G
NM_001382713.1:c.716A>G
NM_001927.4:c.986A>GMANE SELECT
NP_001369637.1:p.Gln328Arg
NP_001369639.1:p.Gln329Arg
NP_001369640.1:p.Gln329Arg
NP_001369641.1:p.Gln329Arg
NP_001369642.1:p.Gln239Arg
NP_001918.3:p.Gln329Arg
NP_001918.3:p.Gln329Arg
LRG_380t1:c.986A>G
LRG_380:g.7540A>G
LRG_380p1:p.Gln329Arg
NC_000002.11:g.220285638A>G
NM_001927.3:c.986A>G

Protein change:

Q239R

Molecular consequence:

NM_001382709.1:c.736-568A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001382708.1:c.983A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382710.1:c.986A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382711.1:c.986A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382712.1:c.986A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001382713.1:c.716A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001927.4:c.986A>G - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004596542	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 31, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004596542

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 31, 2023)

germline

clinical testing

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

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

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, SCV004596542.1

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

Description

This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 329 of the DES protein (p.Gln329Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DES-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on DES protein function. 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.

#	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: Mar 5, 2024

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