VCV000044265.51 - ClinVar

NM_001927.4(DES):c.638C>T (p.Ala213Val)

Germline

Classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

(25)

Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(10); Likely benign(6)

criteria provided, conflicting classifications

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_001927.4(DES):c.638C>T (p.Ala213Val)

Variation ID: 44265 Accession: VCV000044265.51

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q35 2: 219420154 (GRCh38) [ NCBI UCSC ] 2: 220284876 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Oct 19, 2013	May 1, 2024	Feb 1, 2024

HGVS

Nucleotide	Protein	Molecular consequence
NM_001927.4:c.638C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001918.3:p.Ala213Val	missense
NC_000002.12:g.219420154C>T
NC_000002.11:g.220284876C>T
NG_008043.1:g.6778C>T
LRG_380:g.6778C>T
LRG_380t1:c.638C>T	LRG_380p1:p.Ala213Val
	P17661:p.Ala213Val

... more HGVS ... less HGVS

Protein change

A213V

Other names

Canonical SPDI

NC_000002.12:219420153:C:T

Functional consequence Help The effect of the variant on RNA or protein function, based on experimental evidence from submitters.

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.00559 (T)

Allele frequency Help The frequency of the allele represented by this VCV record.

1000 Genomes Project 30x 0.00547

1000 Genomes Project 0.00559

The Genome Aggregation Database (gnomAD), exomes 0.00921

Trans-Omics for Precision Medicine (TOPMed) 0.00963

Exome Aggregation Consortium (ExAC) 0.01015

The Genome Aggregation Database (gnomAD) 0.01015

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.01053

Links

dbSNP: rs41272699 ClinGen: CA133860 UniProtKB: P17661#VAR_042451 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
DES		-	-	GRCh38 GRCh37	1064	1110

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
not specified	Benign/Likely benign (9)	criteria provided, multiple submitters, no conflicts	Sep 3, 2018	RCV000037245.36
not provided	Benign (6)	criteria provided, multiple submitters, no conflicts	Oct 26, 2023	RCV000056805.28
Congenital diaphragmatic hernia	Uncertain significance (1)	criteria provided, single submitter	Mar 3, 2015	RCV000203295.9
Myofibrillar myopathy	Pathogenic (1)	no assertion criteria provided	Aug 16, 2016	RCV000239721.9
Cardiovascular phenotype	Benign (1)	criteria provided, single submitter	Sep 15, 2015	RCV000250294.11
Myofibrillar Myopathy, Dominant	Likely benign (1)	criteria provided, single submitter	Jun 14, 2016	RCV000263666.13
Dilated cardiomyopathy 1I	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000313133.14
Neurogenic scapuloperoneal syndrome, Kaeser type	Likely benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000367823.13
Desmin-related myofibrillar myopathy	Benign/Likely benign (3)	criteria provided, multiple submitters, no conflicts	Feb 1, 2024	RCV001083932.20
Cardiomyopathy	Likely benign (1)	criteria provided, single submitter	Mar 15, 2023	RCV001171067.12

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	More information Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Mar 03, 2015)	criteria provided, single submitter (Beck et al. (Am J Med Genet A 2015)) Method: research	Diaphragmatic hernia 1 (Autosomal dominant inheritance) Affected status: yes, no Allele origin: germline	Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine Accession: SCV000258325.1 First in ClinVar: Jan 10, 2016 Last updated: Jan 10, 2016	Publications: PubMed (1) PubMed: 25736269 Comment: It is unclear whether these changes, alone or in aggregate, are contributing to the development of CDH in this family. Observation 1: Number of individuals with the variant: 2 Family history: yes Sex: male Ethnicity/Population group: Caucasian Observation 2: Number of individuals with the variant: 1 Sex: male Ethnicity/Population group: Caucasian Comment on evidence: The medical evaluation of this individual without CDH is ongoing.
Likely benign (Aug 01, 2017)	criteria provided, single submitter (Athena Diagnostics Criteria) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Athena Diagnostics Accession: SCV000613090.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016	Publications: PubMed (9) PubMed: 16865695‚ 20474083‚ 22215463‚ 25214167‚ 21842594‚ 23168288‚ 17325244‚ 16519886‚ 16217025
Benign (Oct 26, 2023)	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process 2024) Method: clinical testing	not provided Affected status: unknown Allele origin: germline	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV000885275.9 First in ClinVar: Oct 19, 2013 Last updated: Feb 20, 2024
Benign (Sep 15, 2015)	criteria provided, single submitter (Ambry Variant Classification Scheme 2023) Method: clinical testing	Cardiovascular phenotype Affected status: unknown Allele origin: germline	Ambry Genetics Accession: SCV000318135.7 First in ClinVar: Oct 02, 2016 Last updated: May 01, 2024	Comment: This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation … (more) This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. (less)
Benign (Jun 24, 2013)	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013)) Method: research	not specified Affected status: unknown Allele origin: unknown	Biesecker Lab/Clinical Genomics Section, National Institutes of Health Study: ClinSeq Accession: SCV000051520.1 First in ClinVar: Jun 04, 2015 Last updated: Jun 04, 2015 Comments (2): The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for … (more) The study set was not selected for affection status in relation to any cancer. Pathogenicity categories were based on literature curation. See Pubmed ID:23861362 for details. (less) Medical sequencing	Number of individuals with the variant: 22
Benign (-)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	NOT SPECIFIED Affected status: unknown Allele origin: germline	PreventionGenetics, part of Exact Sciences Accession: SCV000308542.1 First in ClinVar: Oct 02, 2016 Last updated: Oct 02, 2016
Benign (Jun 04, 2013)	criteria provided, single submitter (EGL Classification Definitions 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Eurofins Ntd Llc (ga) Accession: SCV000111847.8 First in ClinVar: Jan 17, 2014 Last updated: May 03, 2018	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES Number of individuals with the variant: 2 Sex: mixed
Benign (Sep 03, 2018)	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015) Method: clinical testing	not specified Affected status: unknown Allele origin: germline	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV000919258.1 First in ClinVar: Jun 03, 2019 Last updated: Jun 03, 2019	Publications: PubMed (10) PubMed: 17325244‚ 14724127‚ 16828798‚ 21842594‚ 16217025‚ 16865695‚ 20474083‚ 16519886‚ 23168288‚ 22215463 Comment: Variant summary: DES c.638C>T (p.Ala213Val) results in a non-conservative amino acid change located in the Intermediate filament, rod domain of the encoded protein sequence. Four … (more) Variant summary: DES c.638C>T (p.Ala213Val) results in a non-conservative amino acid change located in the Intermediate filament, rod domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0094 in 278984 control chromosomes in the gnomAD database, including 28 homozygotes. The observed variant frequency is approximately 375 fold of the estimated maximal expected allele frequency for a pathogenic variant in DES causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. c.638C>T has been reported in the literature in individuals affected with Cardiomyopathy as well as in controls. In one study, the variant failed to segregate with disease in a family, being found in 4 healthy individuals and was absent in 1 affected individual (Taylor_2007). In functional studies, cells expressing the variant showed normal complete filamentous network (Bar_2005, Goudeau_2006). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as benign. (less)
Benign (Jan 10, 2012)	criteria provided, single submitter (LMM Criteria) Method: clinical testing	not specified Affected status: not provided Allele origin: germline	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine Accession: SCV000060902.5 First in ClinVar: May 03, 2013 Last updated: Oct 02, 2016	Publications: PubMed (5) PubMed: 17325244‚ 16865695‚ 17626518‚ 14724127‚ 15477095 Comment: Ala213Val in exon 2 of DES: This variant has been reported by several studies an d was initially thought to be disease causing (Goldfarb 2004, … (more) Ala213Val in exon 2 of DES: This variant has been reported by several studies an d was initially thought to be disease causing (Goldfarb 2004, Bar 2004, Kostarev a 2006). However, it has been identified in 0.4% (8/2000) of chromosomes from a broad, though clinically and racially unspecified population (dbSNP rs41272699) and in 1.5% (102/7020) of European American chromosomes and 0.4% (14/3738) of Af rican American chromosomes by the NHBLI Exome sequencing project in a clinical c ohort that included individuals with heart disease (http://evs.gs.washington.edu /EVS). With a frequency this high the variant is considered to be benign. (less) Number of individuals with the variant: 64
Benign (Mar 03, 2015)	criteria provided, single submitter (GeneDx Variant Classification Process June 2021) Method: clinical testing	Not Provided Affected status: yes Allele origin: germline	GeneDx Accession: SCV001844700.1 First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021	Comment: This variant is associated with the following publications: (PMID: 33232181, 32105824, 22215463, 25736269, 17325244, 23861362, 20474083, 27618136, 22260945, 16865695, 21842594, 25617006, 23168288)
Likely benign (Mar 15, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Cardiomyopathy Affected status: unknown Allele origin: germline	CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario Accession: SCV001333737.3 First in ClinVar: May 31, 2020 Last updated: Feb 04, 2024
Benign (Feb 01, 2024)	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015)) Method: clinical testing	Desmin-related myofibrillar myopathy Desmin-related myofibrillar myopathy Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases. Affected status: unknown Allele origin: germline	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV000287227.10 First in ClinVar: Jul 01, 2016 Last updated: Feb 28, 2024
Benign (Mar 30, 2023)	criteria provided, single submitter (ACMG Guidelines, 2015) Method: clinical testing	Desmin-related myofibrillar myopathy Affected status: no Allele origin: germline	Molecular Genetics, Royal Melbourne Hospital Additional submitter: Shariant Australia, Australian Genomics Accession: SCV002503635.2 First in ClinVar: Apr 30, 2022 Last updated: Apr 15, 2024	Comment: European (non-Finnish) population allele frequency is 1.5% (rs41272699, 1,953/129,178 alleles, 20 homozygotes in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this … (more) European (non-Finnish) population allele frequency is 1.5% (rs41272699, 1,953/129,178 alleles, 20 homozygotes in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1 (less)
Likely benign (Jun 14, 2016)	criteria provided, single submitter (ICSL Variant Classification 20161018) Method: clinical testing	Myofibrillar Myopathy, Dominant Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427700.2 First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Myofibrillar myopathy 1 Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427701.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (3) PubMed: 16865695‚ 23143191‚ 16217025 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Dilated cardiomyopathy 1I Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427698.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (5) PubMed: 16865695‚ 17626518‚ 17325244‚ 16217025‚ 21842594 Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Likely benign (Apr 27, 2017)	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019) Method: clinical testing	Neurogenic scapuloperoneal syndrome, Kaeser type Affected status: unknown Allele origin: germline	Illumina Laboratory Services, Illumina Accession: SCV000427699.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, … (more) This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (less)
Pathogenic (Aug 16, 2016)	no assertion criteria provided Method: clinical testing	Myofibrillar myopathy Affected status: yes Allele origin: unknown	Wellcome Centre for Mitochondrial Research, Newcastle University Accession: SCV000298017.1 First in ClinVar: Aug 29, 2016 Last updated: Aug 29, 2016	Publications: DOI: 10.1016/j.nmd.2016.08.004 DOI: 10.1016/j.nmd.2016.08.004 Number of individuals with the variant: 2
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Genome Diagnostics Laboratory, University Medical Center Utrecht Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001932939.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001975788.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Clinical Genetics, Academic Medical Center Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001922672.1 First in ClinVar: Sep 26, 2021 Last updated: Sep 26, 2021
Benign (-)	no assertion criteria provided Method: clinical testing	not specified Affected status: yes Allele origin: germline	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001955208.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC) Additional submitter: Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV002036158.1 First in ClinVar: Dec 18, 2021 Last updated: Dec 18, 2021
Likely benign (-)	no assertion criteria provided Method: clinical testing	not provided Affected status: yes Allele origin: germline	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen Study: VKGL Data-share Consensus Accession: SCV001740997.3 First in ClinVar: Jul 07, 2021 Last updated: Sep 08, 2021
not provided (-)	no classification provided Method: not provided	not provided Affected status: not provided Allele origin: not provided	Epithelial Biology; Institute of Medical Biology, Singapore Accession: SCV000087918.1 First in ClinVar: Oct 19, 2013 Last updated: Oct 19, 2013
click to load more click to collapse

Comment:

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.

Comment:

Variant summary: DES c.638C>T (p.Ala213Val) results in a non-conservative amino acid change located in the Intermediate filament, rod domain of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0094 in 278984 control chromosomes in the gnomAD database, including 28 homozygotes. The observed variant frequency is approximately 375 fold of the estimated maximal expected allele frequency for a pathogenic variant in DES causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is benign. c.638C>T has been reported in the literature in individuals affected with Cardiomyopathy as well as in controls. In one study, the variant failed to segregate with disease in a family, being found in 4 healthy individuals and was absent in 1 affected individual (Taylor_2007). In functional studies, cells expressing the variant showed normal complete filamentous network (Bar_2005, Goudeau_2006). Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments. Based on the evidence outlined above, the variant was classified as benign.

Comment:

Ala213Val in exon 2 of DES: This variant has been reported by several studies an d was initially thought to be disease causing (Goldfarb 2004, Bar 2004, Kostarev a 2006). However, it has been identified in 0.4% (8/2000) of chromosomes from a broad, though clinically and racially unspecified population (dbSNP rs41272699) and in 1.5% (102/7020) of European American chromosomes and 0.4% (14/3738) of Af rican American chromosomes by the NHBLI Exome sequencing project in a clinical c ohort that included individuals with heart disease (http://evs.gs.washington.edu /EVS). With a frequency this high the variant is considered to be benign.

Comment:

European (non-Finnish) population allele frequency is 1.5% (rs41272699, 1,953/129,178 alleles, 20 homozygotes in gnomAD v2.1). Based on the classification scheme RMH ACMG Guidelines v1.1.1, this variant is classified as Benign. Following criteria met: BA1

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Germline Functional Evidence

There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Mitochondrial dysfunction in myofibrillar myopathy.	Vincent AE	Neuromuscular disorders : NMD	2016	DOI: 10.1016/j.nmd.2016.08.004
MotorPlex provides accurate variant detection across large muscle genes both in single myopathic patients and in pools of DNA samples.	Savarese M	Acta neuropathologica communications	2014	PMID: 25214167
Desmin mutations and arrhythmogenic right ventricular cardiomyopathy.	Lorenzon A	The American journal of cardiology	2013	PMID: 23168288
Desminopathies: pathology and mechanisms.	Clemen CS	Acta neuropathologica	2013	PMID: 23143191
Recurrent and founder mutations in the Netherlands: the cardiac phenotype of DES founder mutations p.S13F and p.N342D.	van Spaendonck-Zwarts KY	Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation	2012	PMID: 22215463
Desmin A213V substitution represents a rare polymorphism but not a mutation and is more prevalent in patients with heart dilation of various origins.	Kostareva A	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology	2011	PMID: 21842594
A novel custom resequencing array for dilated cardiomyopathy.	Zimmerman RS	Genetics in medicine : official journal of the American College of Medical Genetics	2010	PMID: 20474083
Prevalence of desmin mutations in dilated cardiomyopathy.	Taylor MR	Circulation	2007	PMID: 17325244
Desmin mutations in a St. Petersburg cohort of cardiomyopathies.	Kostareva A	Acta myologica : myopathies and cardiomyopathies : official journal of the Mediterranean Society of Myology	2006	PMID: 17626518
Variable pathogenic potentials of mutations located in the desmin alpha-helical domain.	Goudeau B	Human mutation	2006	PMID: 16865695
Impact of disease mutations on the desmin filament assembly process.	Bär H	Journal of molecular biology	2006	PMID: 16828798
Forced expression of desmin and desmin mutants in cultured cells: impact of myopathic missense mutations in the central coiled-coil domain on network formation.	Bär H	Experimental cell research	2006	PMID: 16519886
Severe muscle disease-causing desmin mutations interfere with in vitro filament assembly at distinct stages.	Bär H	Proceedings of the National Academy of Sciences of the United States of America	2005	PMID: 16217025
The biology of desmin filaments: how do mutations affect their structure, assembly, and organisation?	Bär H	Journal of structural biology	2004	PMID: 15477095
Desmin myopathy.	Goldfarb LG	Brain : a journal of neurology	2004	PMID: 14724127
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=DES	-	-	-	-
click to load more click to collapse

Text-mined citations for rs41272699 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Nov 25, 2024

ClinVar Genomic variation as it relates to human health

NM_001927.4(DES):c.638C>T (p.Ala213Val)

Variant Details

Genes

Conditions - Germline

Submissions - Germline

Germline Functional Evidence

Citations for germline classification of this variant

Text-mined citations for rs41272699 ...