NM_001927.4(DES):c.1064G>C (p.Arg355Pro) AND Desmin-related myofibrillar myopathy

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

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 23, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000799745.15

Allele description

NM_001927.4(DES):c.1064G>C (p.Arg355Pro)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.1064G>C (p.Arg355Pro)

Other names:

NM_001927.3:c.1064G>C(p.Arg355Pro)

HGVS:

NC_000002.12:g.219421380G>C
NG_008043.1:g.8004G>C
NM_001927.4:c.1064G>CMANE SELECT
NP_001918.3:p.Arg355Pro
LRG_380t1:c.1064G>C
LRG_380:g.8004G>C
NC_000002.11:g.220286102G>C
NC_000002.11:g.220286102G>C
NM_001927.3:c.1064G>C
P17661:p.Arg355Pro

Protein change:

R355P

Links:

UniProtKB: P17661#VAR_042455; dbSNP: rs61368398

NCBI 1000 Genomes Browser:

rs61368398

Molecular consequence:

NM_001927.4:c.1064G>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

Homo sapiens ribosomal protein S13 (RPS13), mRNA
Homo sapiens ribosomal protein S13 (RPS13), mRNA
gi|1520685461|ref|NM_001017.3|

Nucleotide
beta-Mannosidase
beta-Mannosidase
An enzyme that catalyzes the hydrolysis of terminal, non-reducing beta-D-mannose residues in beta-D-mannosides. The enzyme plays a role in the lysosomal degradation of the N-g...<br/>Year introduced: 2004

MeSH
Consensus Development Conference, NIH [Publication Type]
Consensus Development Conference, NIH [Publication Type]
Official statements of the finding or recommendations expressing the outcome from a conference sponsored by NIH.<br/>Year introduced: 2008(2005)

MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000787471	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 16, 2018)	germline	curation	PubMed (2) [See all records that cite these PMIDs] 20696008, 25741868
SCV000939421	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 23, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 16009553, 20696008, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000787471

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 16, 2018)

germline

curation

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

SCV000939421

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 23, 2023)

germline

clinical testing

PubMed (3)
[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, curation

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

A novel desmin R355P mutation causes cardiac and skeletal myopathy.

Fidziańska A, Kotowicz J, Sadowska M, Goudeau B, Walczak E, Vicart P, Hausmanowa-Petrusewicz I.

Neuromuscul Disord. 2005 Aug;15(8):525-31.

PubMed [citation]

PMID:: 16009553

See all PubMed Citations (4)

Details of each submission

From SIB Swiss Institute of Bioinformatics, SCV000787471.1

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

Description

This variant is interpreted as a Likely Pathogenic, for Myopathy, myofibrillar, 1, Autosomal Dominant inheritance. The following ACMG Tag(s) were applied: PM2 => Absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium. PS3 => Well-established functional studies show a deleterious effect (PMID:20696008).

#	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

From Invitae, SCV000939421.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change replaces arginine, which is basic and polar, with proline, which is neutral and non-polar, at codon 355 of the DES protein (p.Arg355Pro). 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. Experimental studies have shown that this missense change affects DES function (PMID: 20696008). 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: 66389). This missense change has been observed in individuals with cardiac and skeletal myopathy (PMID: 16009553, 20696008). This variant is not present in population databases (gnomAD no frequency).

#	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 16, 2024

ClinVar

Relating variation to medicine