ClinVar Miner

Submissions for variant NM_000310.4(PPT1):c.888G>A (p.Trp296Ter)

dbSNP: rs386833670
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001753468 SCV001985480 uncertain significance not provided 2021-02-18 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Nonsense variant predicted to result in protein truncation as the last 11 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; Reported in a patient with late-infantile NCL who harbored a second variant in PPT1; however, segregation analysis to determine phase was not provided (Das et al., 1998); Reported in a patient with late-infantile NCL who had reduced PPT protein level who harbored a second variant in PPT1; however, segregation analysis to determine phase of the variants was not provided (Das et al., 2001); This variant is associated with the following publications: (PMID: 8004106, 14997939, 12125808, 15965709, 9664077, 11440996, 10649502, 11332767, 11073228)
Invitae RCV000049630 SCV004398744 likely pathogenic Neuronal ceroid lipofuscinosis 1 2023-11-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Trp296*) in the PPT1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 11 amino acid(s) of the PPT1 protein. This variant is present in population databases (rs386833670, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 9664077). ClinVar contains an entry for this variant (Variation ID: 56219). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM) RCV000049630 SCV000082037 probable-pathogenic Neuronal ceroid lipofuscinosis 1 no assertion criteria provided not provided Converted during submission to Likely pathogenic.

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