ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.4490G>A (p.Arg1497Gln) (rs727505037)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000157198 SCV000206922 uncertain significance Primary dilated cardiomyopathy 2014-07-16 no assertion criteria provided clinical testing
Invitae RCV000641822 SCV000763472 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-12-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1497 of the DSP protein (p.Arg1497Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs727505037, ExAC 0.03%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 179668). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000156464 SCV000206183 uncertain significance not specified 2019-02-28 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Arg1497Gln va riant in DSP has been identified in 1 individual with DCM. It has also been iden tified in 0.015% (5/33508) of Latino chromosomes by gnomAD (http://gnomad.broadi nstitute.org). Computational prediction tools and conservation analysis suggest that this variant may not impact the protein, though this information is not pre dictive enough to rule out pathogenicity. In summary, while the clinical signifi cance of this variant is uncertain, its frequency in the general population sugg ests that it is more likely to be benign. ACMG/AMP Criteria applied: BP4.
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000156464 SCV000740330 uncertain significance not specified 2016-10-31 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000577979 SCV000679898 uncertain significance Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578033 SCV000679899 uncertain significance Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis 2017-08-01 criteria provided, single submitter clinical testing
Phosphorus, Inc. RCV000578111 SCV000679900 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma 2017-08-01 criteria provided, single submitter clinical testing

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.