ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.1873C>T (p.Gln625Ter) (rs876657638)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000214415 SCV000271215 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2015-10-15 criteria provided, single submitter clinical testing The p.Gln625X variant in DSP has been reported in 1 individual with ARVC (Quarta 2011) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 625 which is predicted to lead to a truncated or absent protein. Frameshift and nonsense variants in DSP have been reported in patients with ARVC (http://arvcdatabase.info/), but recent evidence supports that they can also cause DCM (Pugh 2014). In summary, although additio nal studies are required to fully establish its clinical significance, the p.Gln 625X variant is likely pathogenic.
Invitae RCV000813995 SCV000954382 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-12-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln625*) in the DSP gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 21606390). ClinVar contains an entry for this variant (Variation ID: 228253). Loss-of-function variants in DSP are known to be pathogenic (PMID: 20716751, 24503780, 25227139). For these reasons, this variant has been classified as Pathogenic.

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