ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.916G>A (p.Ala306Thr) (rs368193211)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000038120 SCV000061786 uncertain significance not specified 2018-04-10 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
GeneDx RCV000766873 SCV000233572 uncertain significance not provided 2017-02-08 criteria provided, single submitter clinical testing p.Ala306Thr (A306T) GCT>ACT: c.916 G>A in exon 7 of the DSP gene (NM_004415.2). A variant of unknown significance has been identified in the DSP gene. The A306T variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The A306T variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The A306T variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved through platypus. Another missense mutation in a nearby residue (S299R) has been reported in association with ARVC, supporting the functional importance of this region of the protein. Nevertheless, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in CARDIOMYOPATHY panel(s).
Invitae RCV000527493 SCV000641362 uncertain significance Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-01-23 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 306 of the DSP protein (p.Ala306Thr). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs368193211, ExAC 0.03%). This variant has been reported in an individual who experienced a sudden cardiac death (PMID: 25447171). ClinVar contains an entry for this variant (Variation ID: 44981). 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 tolerated, but these predictions have not been confirmed by published functional studies. In summary, this variant is a rare missense change that is not predicted to affect protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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.