Total submissions: 8
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000009454 | SCV000220758 | likely pathogenic | Neuronal ceroid lipofuscinosis 1 | 2014-09-30 | criteria provided, single submitter | literature only | |
| Gene |
RCV000188716 | SCV000242340 | pathogenic | not provided | 2018-11-21 | criteria provided, single submitter | clinical testing | The L10X nonsense variant in the PPT1 gene has been reported previously in several families with infantile or juvenile neuronal ceroid lipofuscinosis (NCL) who had a second pathogenic variant on the opposite allele (Mitchison et al., 1998; Miller et al., 2013). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Functional analysis showed L10X is associated with decreased mRNA and enzyme activity levels (Das et al., 2001; Miller et al., 2013). |
| Invitae | RCV000009454 | SCV000550823 | pathogenic | Neuronal ceroid lipofuscinosis 1 | 2019-12-10 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Leu10*) in the PPT1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs137852699, ExAC 0.01%). This variant has been observed in individuals affected with juvenile or infantile neuronal ceroid lipofuscinosis (PMID: 9425237, 23539563, 9664077). ClinVar contains an entry for this variant (Variation ID: 8903). Loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943). For these reasons, this variant has been classified as Pathogenic. |
| Ambry Genetics | RCV000715556 | SCV000846385 | pathogenic | History of neurodevelopmental disorder | 2016-05-12 | criteria provided, single submitter | clinical testing | Alterations resulting in premature truncation (e.g.reading frame shift, nonsense) |
| EGL Genetic Diagnostics, |
RCV000188716 | SCV000854968 | pathogenic | not provided | 2017-09-29 | criteria provided, single submitter | clinical testing | |
| Integrated Genetics/Laboratory Corporation of America | RCV000009454 | SCV000920081 | pathogenic | Neuronal ceroid lipofuscinosis 1 | 2017-12-15 | criteria provided, single submitter | clinical testing | Variant summary: The PPT1 c.29T>A (p.Leu10X) variant results in a premature termination codon, predicted to cause a truncated or absent PPT1 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One functional study determined less than 10% PPT activity in PBLs in a patient carrying this mutation (Mitchison_1998). One truncation downstream of this position has been classified as pathogenic by our laboratory (e.g. c.451C>T, p.Arg151X). One in silico tool predicts a damaging outcome for this variant. This variant was found in 20/276316 control chromosomes (gnomAD) at a frequency of 0.0000724, which does not exceed the estimated maximal expected allele frequency of a pathogenic PPT1 variant (0.0007331). This variant has been reported in multiple patients with NCL, in both homozygotes and heterozygotes (Das_1998, Mitchison_1998, Stephenson_1999). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic/pathogenic. Taken together, this variant is classified as pathogenic. |
| Baylor Genetics | RCV000009454 | SCV001162888 | pathogenic | Neuronal ceroid lipofuscinosis 1 | criteria provided, single submitter | clinical testing | ||
| OMIM | RCV000009454 | SCV000029672 | pathogenic | Neuronal ceroid lipofuscinosis 1 | 1998-02-01 | no assertion criteria provided | literature only |