ClinVar Miner

Submissions for variant NM_001927.4(DES):c.638C>T (p.Ala213Val) (rs41272699)

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Total submissions: 17
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000037245 SCV000051520 benign not specified 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037245 SCV000060902 benign not specified 2012-01-10 criteria provided, single submitter clinical testing 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.
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000037245 SCV000111847 benign not specified 2013-06-04 criteria provided, single submitter clinical testing
Lupski Lab, Baylor-Hopkins CMG, Baylor College of Medicine RCV000203295 SCV000258325 uncertain significance Congenital diaphragmatic hernia 2015-03-03 criteria provided, single submitter research It is unclear whether these changes, alone or in aggregate, are contributing to the development of CDH in this family.
Invitae RCV001083932 SCV000287227 benign Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2019-12-31 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000037245 SCV000308542 benign not specified criteria provided, single submitter clinical testing
Ambry Genetics RCV000250294 SCV000318135 benign Cardiovascular phenotype 2015-09-15 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000313133 SCV000427698 likely benign Dilated cardiomyopathy 1I 2017-04-27 criteria provided, single submitter clinical testing 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.
Illumina Clinical Services Laboratory,Illumina RCV000367823 SCV000427699 likely benign Neurogenic scapuloperoneal syndrome, Kaeser type 2017-04-27 criteria provided, single submitter clinical testing 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.
Illumina Clinical Services Laboratory,Illumina RCV000263666 SCV000427700 likely benign Myofibrillar Myopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000318781 SCV000427701 likely benign Myofibrillar myopathy 1 2017-04-27 criteria provided, single submitter clinical testing 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.
Athena Diagnostics Inc RCV000037245 SCV000613090 likely benign not specified 2017-08-01 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000037245 SCV000885275 benign not specified 2018-07-05 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000037245 SCV000919258 benign not specified 2018-09-03 criteria provided, single submitter clinical testing 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.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV001171067 SCV001333737 benign Cardiomyopathy 2018-10-19 criteria provided, single submitter clinical testing
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056805 SCV000087918 not provided not provided no assertion provided not provided
Wellcome Centre for Mitochondrial Research,Newcastle University RCV000239721 SCV000298017 pathogenic Myofibrillar myopathy 2016-08-16 no assertion criteria provided clinical testing

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