ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.928dup (p.Glu310fs) (rs794728137)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Division of Human Genetics,Children's Hospital of Philadelphia RCV000477886 SCV000536704 likely pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8; Epidermolysis bullosa, lethal acantholytic; Skin fragility woolly hair syndrome; Keratosis palmoplantaris striata II; Cardiomyopathy, dilated, with woolly hair, keratoderma, and tooth agenesis 2014-11-06 no assertion criteria provided research
GeneDx RCV000181358 SCV000233659 pathogenic not provided 2017-08-11 criteria provided, single submitter clinical testing The c.928dupG pathogenic variant in the DSP gene has previously been reported in one pediatric patient with sudden cardiac arrest/death (Li et al., 2015); however no additional clinical or segregation data was provided. In addition, it has been observed to segregate with a DCM phenotype in at least one affected relative from a family tested at GeneDx. This variant causes a shift in reading frame starting at codon Glutamic Acid 310, changing it to a Glycine, and creating a premature stop codon at position 13 of the new reading frame, denoted p.Glu310GlyfsX13. This pathogenic variant is expected to result in either an abnormal, truncated protein product or loss of protein from this allele through nonsense-mediated mRNA decay. Multiple other downstream frameshift variants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.928dupG 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, c.928dupG in the DSP gene is interpreted as a pathogenic variant.
Invitae RCV000559042 SCV000639748 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-02-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Glu310Glyfs*13) 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 reported in individuals affected with arrhythmogenic right ventricular cardiomyopathy (PMID: 26187847, 28527814). ClinVar contains an entry for this variant (Variation ID: 199916). 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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