NM_001927.4(DES):c.404C>T (p.Ala135Val) AND not provided

Germline classification:: Uncertain significance (5 submissions)
Last evaluated:: Apr 3, 2024
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000725598.26

Allele description [Variation Report for NM_001927.4(DES):c.404C>T (p.Ala135Val)]

NM_001927.4(DES):c.404C>T (p.Ala135Val)

Gene:

DES:desmin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q35

Genomic location:

Preferred name:

NM_001927.4(DES):c.404C>T (p.Ala135Val)

HGVS:

NC_000002.12:g.219418866C>T
NG_008043.1:g.5490C>T
NM_001927.4:c.404C>TMANE SELECT
NP_001918.3:p.Ala135Val
LRG_380t1:c.404C>T
LRG_380:g.5490C>T
NC_000002.11:g.220283588C>T
NM_001927.3:c.404C>T

Protein change:

A135V

Links:

dbSNP: rs546741834

NCBI 1000 Genomes Browser:

rs546741834

Molecular consequence:

NM_001927.4:c.404C>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000338039	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (May 16, 2018)	germline	clinical testing	Citation Link,
SCV000618838	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Apr 3, 2024)	germline	clinical testing	Citation Link,
SCV002049798	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2021)	Uncertain significance (Oct 29, 2020)	germline	clinical testing	Citation Link,
SCV003829061	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Sep 13, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV004225993	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Dec 7, 2022)	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	4	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

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

Details of each submission

From Eurofins Ntd Llc (ga), SCV000338039.4

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

#	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		3	not provided	not provided	not provided

From GeneDx, SCV000618838.5

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

Description

In silico analysis supports that this missense variant does not alter protein structure/function; In vitro studies confirmed that DES-A135V does not affect desmin filament formation (PMID: 36497166); This variant is associated with the following publications: (PMID: 26807690, 36497166)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV002049798.1

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

Description

The DES c.404C>T; p.Ala135Val variant (rs546741834), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 227281). This variant is found in the South Asian population with an allele frequency of 0.2% (46/24592 alleles, including 0 homozygotes) in the Genome Aggregation Database. The alanine at codon 135 is highly conserved, but computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.2). Due to limited information, the clinical significance of the p.Ala135Val variant is uncertain at this time. Gene Statement: Pathogenic germline variants in DES are predominantly inherited in an autosomal dominant manner, and are associated with myofibrillar myopathy 1/desminopathy (MIM: 601419). Rare observations associated with neurogenic scapuloperoneal syndrome, Kaeser type (MIM: 181400) and non-syndromic dilated cardiomyopathy 1I (MIM: 604765) have been reported.

#	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 Revvity Omics, Revvity, SCV003829061.2

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

#	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 Mayo Clinic Laboratories, Mayo Clinic, SCV004225993.1

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

Description

BP4

#	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		1	not provided	not provided	not provided

Last Updated: Nov 3, 2024

ClinVar

Relating variation to medicine