ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.3865C>T (p.Gln1289Ter) (rs778178956)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000435304 SCV000530007 likely pathogenic not provided 2016-07-18 criteria provided, single submitter clinical testing The Q1289X variant in the DSP gene has not been reported as a pathogenic variant or as a benign variant to our knowledge. Q1289X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other downstream nonsense variants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the Q1289X 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.In summary, Q1289X in the DSP gene is expected to be pathogenic.
Ambry Genetics RCV000617648 SCV000739866 pathogenic Cardiovascular phenotype 2017-10-17 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense),Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000811101 SCV000951349 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-11-13 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1289*) in the DSP gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs778178956, ExAC 0.01%). This variant has not been reported in the literature in individuals with DSP-related disease. ClinVar contains an entry for this variant (Variation ID: 387849). 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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