ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8357A>T (p.Lys2786Met)

dbSNP: rs794728134
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
GeneDx RCV000181350 SCV000233649 uncertain significance not provided 2013-04-02 criteria provided, single submitter clinical testing p.Lys2786Met (AAG>ATG): c.8357 A>T in exon 24 of the DSP gene (NM_004415.2). The Lys2786Met variant in the DSP gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Lys2786Met results in a non-conservative amino acid substitution of a positively charged Lysine with a non-polar Methionine at a position that is well conserved in evolution. The Lys2786Met variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Nevertheless, no mutations in nearby codons have been reported in association with ARVC. With the clinical and molecular information available at this time, we cannot definitively determine if Lys2786Met is a disease-causing mutation or a rare benign variant. The variant is found in ARVC panel(s).
Labcorp Genetics (formerly Invitae), Labcorp RCV005222797 SCV005863195 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2025-01-31 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with methionine, which is neutral and non-polar, at codon 2786 of the DSP protein (p.Lys2786Met). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with DSP-related conditions. ClinVar contains an entry for this variant (Variation ID: 199910). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.