ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.381-2A>G (rs1554902052)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000670849 SCV000795760 likely pathogenic Ceroid lipofuscinosis neuronal 2 2017-11-17 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000589489 SCV000696664 likely pathogenic Neuronal ceroid lipofuscinosis 2017-05-01 criteria provided, single submitter clinical testing Variant summary: The TPP1 c.381-2A>G (IVS4-2A>G) variant involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 5/5 splice prediction tools predict significant impact on normal splicing-loss of canonical splicing acceptor site. ESEfinder predicts changes of binding motifs for splicing enhancers. Consistently, Xiong_2015 used computational modeling and predicted variant to induce large splicing changes. However, these predictions have yet to be confirmed by functional studies. This variant is absent in 121164 control chromosomes. The variant of interest has reported in an affected individual with LINCL as compound heterozygote. Taken together, due to lack of clinical and functional evidence, this variant is classified as likely pathogenic.

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