Submissions for variant NM_004415.4(DSP):c.4735C>T (p.Arg1579Trp)

gnomAD frequency: 0.00001  dbSNP: rs755868373

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001042043	SCV001205701	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2023-12-30	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001182918	SCV001348520	uncertain significance	Cardiomyopathy	2023-05-01	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 1579 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 2/250568 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.
Ambry Genetics	RCV003160282	SCV003867609	uncertain significance	Cardiovascular phenotype	2023-03-01	criteria provided, single submitter	clinical testing	The p.R1579W variant (also known as c.4735C>T), located in coding exon 23 of the DSP gene, results from a C to T substitution at nucleotide position 4735. The arginine at codon 1579 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well 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.
GeneDx	RCV003314662	SCV004014151	uncertain significance	not provided	2023-03-01	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Dept of Medical Biology, Uskudar University	RCV003318390	SCV004021975	uncertain significance	Long QT syndrome	2024-01-08	criteria provided, single submitter	research	Criteria: PM2
All of Us Research Program, National Institutes of Health	RCV004004744	SCV004823402	uncertain significance	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2024-01-11	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with tryptophan at codon 1579 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 2/250568 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.