Submissions for variant NM_004415.4(DSP):c.3507C>A (p.Tyr1169Ter)

dbSNP: rs148894066

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218217	SCV000271216	likely pathogenic	Primary dilated cardiomyopathy	2015-02-19	criteria provided, single submitter	clinical testing	The p.Tyr1169X variant in DSP has not been previously reported in individuals wi th cardiomyopathy or in large population studies. This nonsense variant leads to a premature termination codon at position 1169, which is predicted to lead to a truncated or absent protein. Frameshift and nonsense variants in DSP have been well reported in patients with ARVC (http://arvcdatabase.info/), but recent evid ence supports that they can also cause DCM (Pugh 2014). In summary, although add itional studies are required to fully establish its clinical significance, the p .Tyr1169X variant is likely pathogenic.
Juno Genomics, Hangzhou Juno Genomics, Inc	RCV004796108	SCV005416103	likely pathogenic	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis		criteria provided, single submitter	clinical testing	PM2_Supporting+PVS1