NM_001927.4(DES):c.359C>A (p.Ala120Asp) AND Desmin-related myofibrillar myopathy

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 14, 2019
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:: RCV001059305.15

Allele description [Variation Report for NM_001927.4(DES):c.359C>A (p.Ala120Asp)]

NM_001927.4(DES):c.359C>A (p.Ala120Asp)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.359C>A (p.Ala120Asp)

HGVS:

NC_000002.12:g.219418821C>A
NG_008043.1:g.5445C>A
NM_001927.4:c.359C>AMANE SELECT
NP_001918.3:p.Ala120Asp
LRG_380t1:c.359C>A
LRG_380:g.5445C>A
NC_000002.11:g.220283543C>A
NM_001927.3:c.359C>A

Protein change:

A120D

Links:

dbSNP: rs1954373010

NCBI 1000 Genomes Browser:

rs1954373010

Molecular consequence:

NM_001927.4:c.359C>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

Recent activity

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S41 family peptidase [Halotia branconii CENA392]
S41 family peptidase [Halotia branconii CENA392]
gi|2500984633|gnl|PRJNA962858|QI031 5|gb|WGV25460.1|

Protein
LOC100377765 [Saccoglossus kowalevskii]
LOC100377765 [Saccoglossus kowalevskii]
Gene ID:100377765

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001223926	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 14, 2019)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 24200904, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001223926

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 14, 2019)

germline

clinical testing

PubMed (2)
[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

Citations

PubMed

The novel desmin mutant p.A120D impairs filament formation, prevents intercalated disk localization, and causes sudden cardiac death.

Brodehl A, Dieding M, Klauke B, Dec E, Madaan S, Huang T, Gargus J, Fatima A, Saric T, Cakar H, Walhorn V, Tönsing K, Skrzipczyk T, Cebulla R, Gerdes D, Schulz U, Gummert J, Svendsen JH, Olesen MS, Anselmetti D, Christensen AH, Kimonis V, et al.

Circ Cardiovasc Genet. 2013 Dec;6(6):615-23. doi: 10.1161/CIRCGENETICS.113.000103. Epub 2013 Nov 7.

PubMed [citation]

PMID:: 24200904

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, SCV001223926.5

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

Description

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. This variant has been reported to affect DES protein function (PMID:24200904). This variant has been observed in a family affected with arrhythmogenic right ventricular compaction, dilated cardiomyopathy and sudden cardiac death (PMID: 24200904). This variant is not present in population databases (ExAC no frequency). This sequence change replaces alanine with aspartic acid at codon 120 of the DES protein (p.Ala120Asp). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and aspartic acid.

#	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 13, 2024

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