ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.6853C>A (p.Pro2285Thr) (rs377085222)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038078 SCV000061744 uncertain significance not specified 2010-11-15 criteria provided, single submitter clinical testing The Pro2285Thr variant has not been reported in the literature nor has it been d etected in over 170 Caucasian probands tested by our laboratory. Proline (Pro) a t position 2285 is conserved in mammals as well as in several more distantly rel ated species and two computer prediction programs (Polyphen and SIFT) predict th e change to be deleterious. However, one species (stickleback) carries a differ ent amino acid, raising the possibility that a change at this position may be to lerated. In summary, the clinical significance of the Pro2285Thr variant cannot be determined without additional studies.
Invitae RCV000813688 SCV000954057 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-10-01 criteria provided, single submitter clinical testing This sequence change replaces proline with threonine at codon 2285 of the DSP protein (p.Pro2285Thr). The proline residue is highly conserved and there is a small physicochemical difference between proline and threonine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 44942). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.

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.