ClinVar Miner

Submissions for variant NM_001927.4(DES):c.347A>G (p.Asn116Ser) (rs267607499)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000150380 SCV000197520 likely pathogenic Myofibrillar myopathy 1 2014-03-05 criteria provided, single submitter clinical testing The Asn116Ser variant in DES has been reported in 1 Caucasian individual with ea rly onset ARVC and was confirmed to be a de novo occurrence (Klauke 2010). Data from large population studies is insufficient to assess the frequency of this va riant. Functional studies have shown that the Asn116Ser variant impacts protein function (Klauke 2010, Brodehl 2012). However, these in vitro assays may not acc urately represent biological function. Computational prediction tools and conser vation analysis suggest that this variant may impact the protein, though this in formation is not predictive enough to determine pathogenicity. In summary, this variant is likely to be pathogenic, though additional studies are required to fu lly establish its clinical significance.
Invitae RCV000150380 SCV000638118 likely pathogenic Myofibrillar myopathy 1 2017-03-16 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 116 of the DES protein (p.Asn116Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been reported in the literature in two individuals affected with arrythmogenic right ventricular cardiomyopathy (ARVC) (PMID: 20829228, 26676851). In one of these individuals, this variant was found to have arisen de novo (i.e. not present in the parents) (PMID: 20829228). ClinVar contains an entry for this variant (Variation ID: 66411). Experimental studies have shown that this missense change diminishes the capacity of the protein to form functional filaments and instead creates non-functional protein aggregates (PMID: 20829228, 22403400). In summary, this variant is a rare missense change that has been reported in affected individuals and has been shown to have a deleterious effect on protein stability. This evidence indicates that the variant is pathogenic, but additional data is needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Invitae RCV001384253 SCV001583679 pathogenic Myofibrillar myopathy 1; Muscular dystrophy, limb-girdle, type 2R 2020-06-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 116 of the DES protein (p.Asn116Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with DES-related conditions (PMID: 20829228, 26676851, Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 66411). This variant has been reported to affect DES protein function (PMID: 20829228, 22403400). For these reasons, this variant has been classified as Pathogenic.
Epithelial Biology; Institute of Medical Biology, Singapore RCV000056799 SCV000087912 not provided not provided no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.