ClinVar Miner

Submissions for variant NM_000391.4(TPP1):c.311T>A (p.Leu104Ter) (rs202189057)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000189751 SCV000243399 pathogenic not provided 2012-12-11 criteria provided, single submitter clinical testing p.Leu104Stop (TTG>TAG): c.311 T>A in exon 4 of the TPP1 gene (NM_000391.3)The Leu104Stop nonsense mutation in the TPP1 gene, associated with neuronal ceroid lipofuscinosis (NCL), was cited in a published paper reporting on novel human pathological mutations (Kohan et al., 2008). This mutation is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in CHILD-EPI panel(s).
Ambry Genetics RCV000210549 SCV000262853 pathogenic Inborn genetic diseases 2014-04-10 criteria provided, single submitter clinical testing
Invitae RCV000550405 SCV000628909 pathogenic Neuronal ceroid lipofuscinosis 2018-03-20 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu104*) in the TPP1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs202189057, ExAC 0.001%). This variant has been reported as homozygous or compound heterozygous with a second, rare TPP1 allele, in individuals and families affected with neuronal ceroid lipofuscinosis (PMID: 19793312, 23266810, 23539563) and in an individual with focal seizures (PMID: 26795593).  ClinVar contains an entry for this variant (Variation ID: 207561). Loss-of-function variants in TPP1 are known to be pathogenic (PMID: 10330339). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV000984312 SCV001163323 pathogenic Ceroid lipofuscinosis neuronal 2 criteria provided, single submitter clinical testing
Counsyl RCV000984312 SCV001132495 likely pathogenic Ceroid lipofuscinosis neuronal 2 2015-04-01 no assertion criteria provided clinical testing

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