ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5851C>T (p.Arg1951Ter) (rs869025395)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000208287 SCV000263878 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2015-06-08 criteria provided, single submitter clinical testing
GeneDx RCV000427986 SCV000534595 pathogenic not provided 2017-01-16 criteria provided, single submitter clinical testing The R1951X variant in the DSP gene has been reported as a pathogenic variant in and individual with with adiagnosis of DCM and in a individual with a diagnosis of HCM (Cuenca et al., 2016; Bottillo et al., 2016). R1951X is predicted to cause loss of normal protein function by protein truncation. Other downstream nonsense variants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014), suggestingprotein truncation is a mechanism of disease. Lastly, the R1951X variant has not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Project; Exome Variant Server). In summary, R1951X in the DSP gene is interpreted as a pathogenic variant.
Invitae RCV000529617 SCV000639746 pathogenic Arrhythmogenic right ventricular cardiomyopathy, type 8 2017-06-08 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the DSP gene (p.Arg1951*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 921 amino acids of the DSP protein. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an heterozygous individual affected with dilated cardiomyopathy (PMID: 26899768). A different truncation downstream of this variant (c.7901delG) has been determined to be pathogenic (PMID: 11063735). This suggests that deletion of this region of the DSP protein is causative of disease. For these reasons, this variant has been classified as Pathogenic.

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