NM_001927.4(DES):c.61G>A (p.Ala21Thr) AND Desmin-related myofibrillar myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 29, 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:: RCV003778860.2

Allele description [Variation Report for NM_001927.4(DES):c.61G>A (p.Ala21Thr)]

NM_001927.4(DES):c.61G>A (p.Ala21Thr)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.61G>A (p.Ala21Thr)

HGVS:

NC_000002.12:g.219418523G>A
NG_008043.1:g.5147G>A
NG_046330.1:g.18915G>A
NM_001382708.1:c.61G>A
NM_001382709.1:c.61G>A
NM_001382710.1:c.61G>A
NM_001382711.1:c.61G>A
NM_001382712.1:c.61G>A
NM_001382713.1:c.61G>A
NM_001927.4:c.61G>AMANE SELECT
NP_001369637.1:p.Ala21Thr
NP_001369638.1:p.Ala21Thr
NP_001369639.1:p.Ala21Thr
NP_001369640.1:p.Ala21Thr
NP_001369641.1:p.Ala21Thr
NP_001369642.1:p.Ala21Thr
NP_001918.3:p.Ala21Thr
NP_001918.3:p.Ala21Thr
LRG_380t1:c.61G>A
LRG_380:g.5147G>A
LRG_380p1:p.Ala21Thr
NC_000002.11:g.220283245G>A
NM_001927.3:c.61G>A
NM_001927.3:c.61G>A

Protein change:

A21T

Molecular consequence:

NM_001382708.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382709.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382710.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382711.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382712.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001382713.1:c.61G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001927.4:c.61G>A - 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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25549[uid] AND (alive[prop]) (1)
Gene
Slc18a2 solute carrier family 18 member A2 [Rattus norvegicus]
Slc18a2 solute carrier family 18 member A2 [Rattus norvegicus]
Gene ID:25549

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004572596	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Mar 29, 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

SCV004572596

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Mar 29, 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 Labcorp Genetics (formerly Invitae), Labcorp, SCV004572596.1

#	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 alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 21 of the DES protein (p.Ala21Thr). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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. 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. ClinVar contains an entry for this variant (Variation ID: 2440744). This variant has not been reported in the literature in individuals affected with DES-related conditions.

#	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: Oct 8, 2024

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