ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.136G>A (p.Gly46Ser)

gnomAD frequency: 0.00001  dbSNP: rs371517189
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001181049 SCV001346114 uncertain significance Cardiomyopathy 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 46 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 3/206056 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001232032 SCV001404575 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-07-27 criteria provided, single submitter clinical testing
Ambry Genetics RCV002379099 SCV002700326 uncertain significance Cardiovascular phenotype 2021-08-06 criteria provided, single submitter clinical testing The p.G46S variant (also known as c.136G>A), located in coding exon 1 of the DSP gene, results from a G to A substitution at nucleotide position 136. The glycine at codon 46 is replaced by serine, an amino acid with similar properties. This variant was detected in an individual with dilated cardiomyopathy (DCM), who also had a TTN frameshift variant (Klauke B et al. PLoS One, 2017 Dec;12:e0189489). This amino acid position is poorly 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.
All of Us Research Program, National Institutes of Health RCV003995745 SCV004815187 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2023-12-13 criteria provided, single submitter clinical testing This missense variant replaces glycine with serine at codon 46 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 3/206056 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.
Institut für Laboratoriums- und Transfusionsmedizin, Herz- und Diabeteszentrum Nordrhein-Westfalen RCV000491487 SCV000298134 uncertain significance Dilated cardiomyopathy 1S 2016-05-01 no assertion criteria provided clinical testing

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