ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.5680_5683del (p.Ser1894fs) (rs774763657)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000458285 SCV000543241 pathogenic Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-01-24 criteria provided, single submitter clinical testing This sequence change deletes 4 nucleotide from exon 24 of the DSP mRNA (c.5680_5683delAGTC), causing a frameshift at codon 1894. This creates a premature translational stop signal in the last exon of the DSP mRNA (p.Ser1894Leufs*34).  While this is not anticipated to result in nonsense mediated decay, it is expected to result in a truncated DSP protein. While this truncation has not been reported in the literature, a truncating variant located downstream in exon 24 has been reported to be deleterious (PMID: 11063735). For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV000522863 SCV000618362 likely pathogenic not provided 2018-04-23 criteria provided, single submitter clinical testing The novel c.5680_5683delAGTC variant in the DSP gene has not been reported to our knowledge. However, thisvariant causes a shift in reading frame starting at codon serine 1894, changing it to a leucine, and creating a prematurestop codon at position 34 of the new reading frame, denoted p.Ser1894LeufsX34. This likely pathogenic variant isexpected to result in a truncated protein product such that the last 978 amino acids are replaced with 33 incorrectamino acids. Other downstream frameshift variants in the DSP gene have been reported in Human Gene MutationDatabase in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.5680_5683delAGTC varianthas not been observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; ExomeVariant Server).

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