Submissions for variant NM_001927.4(DES):c.38C>T (p.Ser13Phe)

dbSNP: rs62636495

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037240	SCV000060897	pathogenic	Primary dilated cardiomyopathy	2011-09-07	criteria provided, single submitter	clinical testing	The Ser13Phe variant has been reported in several families showing significant s egregation with desmin-related myopathy (> than 10 affected family members posit ive) and was absent from > 400 control chromosomes (Bergman 2007, Pica 2008, van Tintelen 2009). Serine (Ser) at position 13 is highly conserved across evoluti onarily distant species, suggesting that a change in the amino acid may not be t olerated. In addition, in vitro studies show that this variant impacts the stru cture and function of desmin protein (Pica 2008, Sharma 2009). Therefore, the S er13Phe variant meets our criteria for pathogenicity (http://pcpgm.partners.org/ lmm) based on segregation studies, absence from controls, and functional evidenc e.
Baylor Genetics	RCV001389153	SCV000245471	pathogenic	Desmin-related myofibrillar myopathy	2013-11-26	criteria provided, single submitter	clinical testing	This variant has been previously reported as disease-causing and was found once in our laboratory in a 46-year-old male with arrhythmia, hypertrophic cardiomyopathy, EMG evidence of distal myopathy with myotonic discharges, progressive balance issues, short stature, scolisos, small hands, maternal family history of heart problems. Myotonia was likely explained by additional variants in this individual.
Blueprint Genetics	RCV001389153	SCV000263827	pathogenic	Desmin-related myofibrillar myopathy	2014-12-15	criteria provided, single submitter	clinical testing
Eurofins Ntd Llc (ga)	RCV000056801	SCV000332859	pathogenic	not provided	2017-03-02	criteria provided, single submitter	clinical testing
Invitae	RCV001389153	SCV001590419	pathogenic	Desmin-related myofibrillar myopathy	2022-03-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DES function (PMID: 19763525, 22403400). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 44260). This missense change has been observed in individuals with autosomal dominant dilated cardiomyopathy and/or skeletal myopathy (PMID: 17720647, 18061454, 19879535, 23349452, 26097489). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 13 of the DES protein (p.Ser13Phe).
Epithelial Biology; Institute of Medical Biology, Singapore	RCV000056801	SCV000087914	not provided	not provided		no assertion provided	not provided
OMIM	RCV001389153	SCV000188575	pathogenic	Desmin-related myofibrillar myopathy	2009-11-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000056801	SCV001740070	pathogenic	not provided		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000056801	SCV001925003	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000056801	SCV001952696	pathogenic	not provided		no assertion criteria provided	clinical testing