Submissions for variant NM_004415.4(DSP):c.3316G>T (p.Glu1106Ter)

dbSNP: rs1131691673

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493174	SCV000582607	likely pathogenic	not provided	2015-11-09	criteria provided, single submitter	clinical testing	The E1106X variant in the DSP gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. E1106X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the DSP gene have been reported in HGMD in association with ARVC (Stenson et al., 2014). Furthermore, the E1106X variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.
Color Diagnostics, LLC DBA Color Health	RCV003532145	SCV004363357	pathogenic	Cardiomyopathy	2022-05-09	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 23 of the DSP gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual affected with dilated cardiomyopathy (PMID: 32826072). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of DSP function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.