ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.268C>T (p.Gln90Ter) (rs886039343)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000255530 SCV000321563 pathogenic not provided 2018-04-09 criteria provided, single submitter clinical testing Although the Q90X variant in the DSP gene has not been published as pathogenic or been reported as benign to our knowledge, it has been identified in at least four unrelated individuals referred for cardiac genetic testing at GeneDx. Q90X is predicted to cause loss of normal protein function either by protein truncation or nonsense-mediated mRNA decay. Other nonsense variants in the DSP gene have been reported in Human Gene Mutation Database in association with DSP-related disorders (Stenson et al., 2014). Furthermore, the Q90X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). In summary, Q90X in the DSP gene is interpreted as a pathogenic variant.
Invitae RCV000459399 SCV000543247 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-11-28 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal at codon 90 (p.Gln90*) of the DSP gene. It is expected to result in an absent or disrupted protein product. While this particular variant has not been reported in the literature, loss-of-function variants in DSP are known to be pathogenic (PMID: 24503780, 20716751). For these reasons, this variant has been classified as Pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000255530 SCV000883754 pathogenic not provided 2017-10-20 criteria provided, single submitter clinical testing The p.Gln90Ter variant is predicted to result in a truncated or absent protein product. This variant has not been reported in the medical literature; however a similar truncating variant (p.Q51Ter) was reported in one individual with Arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD), whereby electrical abnormalities on electrocardiography and Holter monitoring were proposed as an indicator for high risk patients (te Riele, 2013). This variant is listed in the Genome Aggregation Database (gnomAD) identified on a single chromosome out of 245,444, and has been reported to the ClinVar database as a pathogenic/likely pathogenic variant (Variation ID: 265102). Based on these observations, the p.Gln90Ter variant is considered to be pathogenic.

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