ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.344A>G (p.Asn115Ser)

gnomAD frequency: 0.00003  dbSNP: rs28763958
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000620647 SCV000736767 uncertain significance Cardiovascular phenotype 2022-12-19 criteria provided, single submitter clinical testing The p.N115S variant (also known as c.344A>G), located in coding exon 3 of the DSP gene, results from an A to G substitution at nucleotide position 344. The asparagine at codon 115 is replaced by serine, an amino acid with highly similar properties. This variant has been detected in an individual from a dilated cardiomyopathy cohort (Boen HM et al. J Heart Lung Transplant. 2022 Sep;41(9):1218-1227). 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000811284 SCV000951542 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2023-09-26 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV001187550 SCV001354370 uncertain significance Cardiomyopathy 2023-02-22 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 115 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 been reported in an individual affected dilated cardiomyopathy (PMID: 35581137). This variant has been identified in 16/251460 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.
Loeys Lab, Universiteit Antwerpen RCV001375635 SCV001572560 uncertain significance Primary dilated cardiomyopathy 2021-02-26 criteria provided, single submitter clinical testing This sequence change results in a missense variant in the DSP gene (p.(Asn115Ser)) )), which is a known mechanism (PP2). This variant is present in population databases with a prevalence of 7/121400 in GnomAD). This variant has not been reported in the literature and no functional data are available. Prediction programs show conflicting results ( Align GVGD C0; Polyphen-2-HumDiv probably damaging; Polyphen-2-HumVar probably damaging; SIFT not pathogenic). The variant was identified in a patient with DCM, however no data on segregation are available. In conclusion this variant was classified as a variant of unknown significance according to ACMG-guidelines (insufficient data, criteria for other classification are not met: PP2).
GeneDx RCV000998518 SCV001789161 uncertain significance not provided 2020-01-17 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID#; Landrum et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function
All of Us Research Program, National Institutes of Health RCV004002664 SCV004822031 uncertain significance Arrhythmogenic cardiomyopathy with wooly hair and keratoderma 2024-07-29 criteria provided, single submitter clinical testing This missense variant replaces asparagine with serine at codon 115 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 been reported in an individual affected dilated cardiomyopathy (PMID: 35581137). This variant has been identified in 16/251460 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.
Mayo Clinic Laboratories, Mayo Clinic RCV000998518 SCV005411999 uncertain significance not provided 2023-10-13 criteria provided, single submitter clinical testing

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