ClinVar Miner

Submissions for variant NM_000310.4(PPT1):c.433+1G>A

dbSNP: rs1553167415
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673308 SCV000798495 likely pathogenic Neuronal ceroid lipofuscinosis 1 2018-03-12 criteria provided, single submitter clinical testing
3billion RCV000673308 SCV002572929 pathogenic Neuronal ceroid lipofuscinosis 1 2022-09-01 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site is predicted to alter splicing and result in a loss or disruption of normal protein function. Multiple pathogenic loss-of-function variants are reported downstream of the variant. The variant has been reported to be in trans with a pathogenic variant as either compound heterozygous or homozygous in at least one similarly affected unrelated individual (3billion dataset). The variant has been reported to be associated with PPT1-related disorder (ClinVar ID: VCV000557200). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV000673308 SCV004536868 pathogenic Neuronal ceroid lipofuscinosis 1 2023-10-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 4 of the PPT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943, 21990111). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with neuronal ceroid lipofuscinosis 1 (PMID: 31489614; Invitae). ClinVar contains an entry for this variant (Variation ID: 557200). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.

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