ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.379C>T (p.Arg127Ter) (rs756564767)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000763269 SCV000893912 pathogenic Ceroid lipofuscinosis neuronal 2; Childhood-onset autosomal recessive slowly progressive spinocerebellar ataxia 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000189759 SCV000243407 pathogenic not provided 2018-06-22 criteria provided, single submitter clinical testing The R127X nonsense variant in the TPP1 gene has been reported previously in the homozygous and compound heterozygous state in multiple unrelated individuals with neuronal ceroid lipofuscinosis (Sleat et al., 1999; Kousi et al., 2012; Di Fruscio et al., 2015). This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R127X variant is observed in 11/34420 (0.03%) alleles from individuals of Latino background (Lek et al., 2016). Therefore, we interpret R127X as a pathogenic variant.
Invitae RCV000792396 SCV000931692 pathogenic Neuronal ceroid lipofuscinosis 2018-11-09 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg127*) in the TPP1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs756564767, ExAC 0.01%). This variant has been observed in combination with another TPP1 variant in an individual affected with autosomal recessive neuronal ceroid lipofucinosis (PMID: 10330339). ClinVar contains an entry for this variant (Variation ID: 207569). Loss-of-function variants in TPP1 are known to be pathogenic (PMID: 10330339). For these reasons, this variant has been classified as Pathogenic.

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