ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.423-1G>T (rs1304410089)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000497916 SCV000590153 pathogenic not provided 2017-05-30 criteria provided, single submitter clinical testing Although the c.423-1 G>T variant has not been reported as a pathogenic or benign to our knowledge, functional studies show that a variant at the same nucleotide position, c.423-1 G>A, leads to aberrant spliced mRNA products that lead to a truncated protein (Bauce et al., 2005). Additionally, this nucleotide substitution occurs at a position that is conserved across species. The c.423-1 G>T variant destroys the canonical splice acceptor site in intron 3 and is predicted to cause abnormal gene splicing. This variant is predicted to lead to either an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. Other splice site variants in the DSP gene have been reported in HGMD in association with cardiomyopathy (Stenson et al., 2014). Furthermore, the c.423-1 G>T variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server).
Ambry Genetics RCV000621858 SCV000735571 pathogenic Cardiovascular phenotype 2016-10-25 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Well-characterized mutation at same position,Alterations at the canonical donor/acceptor sites (+/- 1, 2) without other strong (b-level) evidence supporting pathogenicity

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