ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.523C>T (p.Gln175Ter)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000807937 SCV000948017 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-10-24 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln175*) 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 not been reported in the literature in individuals with DSP-related disease. 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.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826163 SCV000967700 likely pathogenic Primary dilated cardiomyopathy; Arrhythmogenic right ventricular cardiomyopathy 2018-05-25 criteria provided, single submitter clinical testing The p.Gln175X variant in DSP has not been previously reported in individuals wit h cardiomyopathy and was absent from large population studies. This nonsense var iant leads to a premature termination codon at position 175, which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the D SP gene is an established disease mechanism for Dilated cardiomyopathy and Arrhy thmogenic right ventricular cardiomyopathy. In summary, although additional stud ies are required to fully establish its clinical significance, the p.Gln175X var iant is likely pathogenic. ACMG/AMP criteria applied: PVS1, PM2.

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