ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.61G>A (p.Glu21Lys)

gnomAD frequency: 0.00001  dbSNP: rs747956457
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000530910 SCV000641331 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-09-23 criteria provided, single submitter clinical testing
Ambry Genetics RCV000619337 SCV000737496 uncertain significance Cardiovascular phenotype 2020-03-27 criteria provided, single submitter clinical testing The p.E21K variant (also known as c.61G>A), located in coding exon 1 of the DSP gene, results from a G to A substitution at nucleotide position 61. The glutamic acid at codon 21 is replaced by lysine, an amino acid with similar properties. This variant co-occurred with a frameshift variant in the DSC2 gene in an individual from an arrhythmogenic right ventricular cardiomyopathy cohort (Castelletti S et al. Int. J. Cardiol., 2017 Dec;249:268-273). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Diagnostics, LLC DBA Color Health RCV001177348 SCV001341545 uncertain significance Cardiomyopathy 2022-09-21 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 21 of the DSP protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 3/224706 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
GeneDx RCV002253507 SCV002525301 uncertain significance not provided 2022-05-09 criteria provided, single submitter clinical testing Has been reported in individuals with ARVC (Castelletti et al., 2017; Ye et al., 2019); Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 31402444, 28527814)

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