ClinVar Miner

Submissions for variant NM_000310.3(PPT1):c.3G>A (p.Met1Ile) (rs386833645)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000049604 SCV000220679 likely pathogenic Ceroid lipofuscinosis neuronal 1 2014-09-08 criteria provided, single submitter literature only
Integrated Genetics/Laboratory Corporation of America RCV000589397 SCV000696512 likely pathogenic Neuronal ceroid lipofuscinosis 2017-06-30 criteria provided, single submitter clinical testing Variant summary: The PPT1 c.3G>A (p.M1I) variant causes a missense change involving the alteration of a highly conserved nucleotide. The variant alters the start codon 3/5 in silico tools predict a damaging outcome for this variant. The M1I displayed almost full activity (87.5% of wild type) as analyzed by overexpression in COS-1 cells, however resulting in low but clinically relevant expression of the normal enzyme (Lyly, 2007; Das, 1998). The c.3G>A was not identified in large, broad control datasets of ExAC and gnomAD (~118264 and ~242968 chrs tested, respectively), but is found in at least three patient with late onset or juvenile NCL (Das, 1998, Hofmann, 1999) and segregated with the disease in one family (Hofmann, 1999). Lastly, clinical diagnostic laboratories/reputable databases classified this variant as Likely Pathogenic. Taken together, this variant is classified as Likely Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049604 SCV000082011 probable-pathogenic Ceroid lipofuscinosis neuronal 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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