Submissions for variant NM_004415.4(DSP):c.3687_3689dup (p.Glu1229dup)

dbSNP: rs1561697838

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001062857	SCV001227680	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2019-11-19	criteria provided, single submitter	clinical testing	This variant, c.3687_3689dup, results in the insertion of 1 amino acid(s) to the DSP protein (p.Glu1229dup), but otherwise preserves the integrity of the reading frame. 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 conditions. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001280685	SCV001467985	uncertain significance	not specified	2020-12-29	criteria provided, single submitter	clinical testing	Variant summary: DSP c.3687_3689dupGGA (p.Glu1229dup) results in an in-frame duplication that is predicted to duplicate one amino acid into the encoded protein. The variant allele was found at a frequency of 1.2e-05 in 250962 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.3687_3689dupGGA in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneDx	RCV001760031	SCV001998306	uncertain significance	not provided	2020-08-20	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In-frame duplication of one amino acid in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
AiLife Diagnostics, AiLife Diagnostics	RCV001760031	SCV002503203	uncertain significance	not provided	2021-12-26	criteria provided, single submitter	clinical testing