Submissions for variant NM_004415.4(DSP):c.6386T>G (p.Ile2129Ser)

dbSNP: rs1401697610

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001180979	SCV001346032	uncertain significance	Cardiomyopathy	2019-11-17	criteria provided, single submitter	clinical testing	This missense variant replaces isoleucine with serine at codon 2129 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has not been identified 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	RCV003284020	SCV004007843	uncertain significance	Cardiovascular phenotype	2023-05-22	criteria provided, single submitter	clinical testing	The p.I2129S variant (also known as c.6386T>G), located in coding exon 24 of the DSP gene, results from a T to G substitution at nucleotide position 6386. The isoleucine at codon 2129 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is conserved. 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.