ClinVar Miner

Submissions for variant NM_000310.4(PPT1):c.665T>C (rs386833661)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001192781 SCV001361119 pathogenic Neuronal ceroid lipofuscinosis 2019-11-01 criteria provided, single submitter clinical testing Variant summary: PPT1 c.665T>C (p.Leu222Pro) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 31368 control chromosomes. c.665T>C has been reported in the literature in multiple individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (Mazzei_2002, Simonati_2009, Santorelli_2013). These data indicate that the variant is very likely to be associated with disease. Simonati et al report that this mutation occurs in the hydrophobic pouch of PPT-1, and the introduction of a proline may hamper the correct folding and therefore the beta-sheet conformation of the protein (Simonati_2009). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit,IRCCS Fondazione Stella Maris RCV001646987 SCV001519267 likely pathogenic Spastic ataxia 2021-07-12 criteria provided, single submitter research
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049621 SCV000082028 probable-pathogenic Neuronal ceroid lipofuscinosis 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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