Submissions for variant NM_001927.4(DES):c.669T>C (p.Ile223=)

gnomAD frequency: 0.02876  dbSNP: rs75882680

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029659	SCV000052311	benign	Cardiomyopathy	2011-08-18	criteria provided, single submitter	curation	Converted during submission to Benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037247	SCV000060904	benign	not specified	2011-09-19	criteria provided, single submitter	clinical testing	Ile223Ile in exon 3 of DES: This variant is classified as benign because it does not change the amino acid and is frequent in the general population (rs7588268, MAF >1%).
Eurofins Ntd Llc (ga)	RCV000037247	SCV000111848	benign	not specified	2013-03-12	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000037247	SCV000150954	benign	not specified	2013-08-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000037247	SCV000308543	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000250651	SCV000317740	benign	Cardiovascular phenotype	2015-12-07	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Illumina Laboratory Services, Illumina	RCV000265756	SCV000427706	benign	Myofibrillar Myopathy, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000320860	SCV000427707	benign	Neurogenic scapuloperoneal syndrome, Kaeser type	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000384969	SCV000427708	likely benign	Dilated cardiomyopathy 1I	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina	RCV000476709	SCV000427709	likely benign	Desmin-related myofibrillar myopathy	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Invitae	RCV000476709	SCV000562344	benign	Desmin-related myofibrillar myopathy	2024-02-01	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000029659	SCV000901595	benign	Cardiomyopathy	2015-09-15	criteria provided, single submitter	clinical testing
GeneDx	RCV001659730	SCV001872012	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001659730	SCV004562781	benign	not provided	2023-03-09	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000037247	SCV001924414	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037247	SCV001955535	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000037247	SCV001976147	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV001659730	SCV002035663	likely benign	not provided		no assertion criteria provided	clinical testing