ClinVar Miner

Submissions for variant NM_001927.4(DES):c.38C>T (p.Ser13Phe) (rs62636495)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare 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 ( lmm) based on segregation studies, absence from controls, and functional evidenc e.
Baylor Genetics RCV000133501 SCV000245471 pathogenic Myofibrillar myopathy 1 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 RCV000133501 SCV000263827 pathogenic Myofibrillar myopathy 1 2014-12-15 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000056801 SCV000332859 pathogenic not provided 2017-03-02 criteria provided, single submitter clinical testing
Invitae RCV001389153 SCV001590419 pathogenic Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2020-03-06 criteria provided, single submitter clinical testing This sequence change replaces serine with phenylalanine at codon 13 of the DES protein (p.Ser13Phe). The serine residue is highly conserved and there is a large physicochemical difference between serine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with autosomal dominant dilated cardiomyopathy and/or skeletal myopathy (PMID: 17720647, 26097489, 18061454, 19879535, 23349452). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 44260). This variant has been reported to affect DES protein function (PMID: 22403400, 19763525). For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056801 SCV000087914 not provided not provided no assertion provided not provided
OMIM RCV000133501 SCV000188575 pathogenic Myofibrillar myopathy 1 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

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