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NM_000391.4(TPP1):c.509-1G>A AND Neuronal ceroid lipofuscinosis

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Feb 18, 2016
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV000586250.4

Allele description [Variation Report for NM_000391.4(TPP1):c.509-1G>A]

NM_000391.4(TPP1):c.509-1G>A

Gene:
TPP1:tripeptidyl peptidase 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000391.4(TPP1):c.509-1G>A
HGVS:
  • NC_000011.10:g.6617154C>T
  • NG_008653.1:g.7308G>A
  • NM_000391.4:c.509-1G>AMANE SELECT
  • LRG_830t1:c.509-1G>A
  • LRG_830:g.7308G>A
  • NC_000011.9:g.6638385C>T
  • NM_000391.3:c.509-1G>A
Links:
dbSNP: rs56144125
NCBI 1000 Genomes Browser:
rs56144125
Molecular consequence:
  • NM_000391.4:c.509-1G>A - splice acceptor variant - [Sequence Ontology: SO:0001574]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis
Synonyms:
Ceroid storage disease
Identifiers:
MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000696665Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Feb 18, 2016) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Late infantile neuronal ceroid lipofuscinosis: mutations in the CLN2 gene and clinical course in Spanish patients.

Pérez-Poyato MS, Marfa MP, Abizanda IF, Rodriguez-Revenga L, Sánchez VC, González MJ, Puñal JE, Pérez AV, González MM, Bermejo AM, Hernández EM, Rosell MJ, Gort L, Milá M.

J Child Neurol. 2013 Apr;28(4):470-8. doi: 10.1177/0883073812448459. Epub 2012 Jul 25.

PubMed [citation]
PMID:
22832778

Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.

Sleat DE, Gin RM, Sohar I, Wisniewski K, Sklower-Brooks S, Pullarkat RK, Palmer DN, Lerner TJ, Boustany RM, Uldall P, Siakotos AN, Donnelly RJ, Lobel P.

Am J Hum Genet. 1999 Jun;64(6):1511-23. Erratum in: Am J Hum Genet. 2004 Dec;75(6):1158.

PubMed [citation]
PMID:
10330339
PMCID:
PMC1377895
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696665.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: TPP1 c.509-1G>A is a splice-site variant that alters a conserved nucleotide. 5/5 in silico tools via Alamut predict this variant to disrupt a canonical acceptor sequence, which has been confirmed by Hartikainen et al (1999) who showed an aberrant splicing pattern. It has been reported in multiple affected individuals with LINCL with nearly absent residual enzyme activity (Perez-Poyato_JCN_2012 and Hartikainen_MGM_1999, respectively). The variant is present in ExAC at low frequency (0.0025%) which does not exceed the maximum frequency for a pathogenic variant in TPP1 gene (0.29%). Lastly, it has been classified as pathogenic via publications and/or reputable databases/clinical laboratories. Taken together, the variant was classified as Pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024