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NM_000391.4(TPP1):c.605C>T (p.Pro202Leu) AND not provided

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 2023
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:
RCV001854254.4

Allele description [Variation Report for NM_000391.4(TPP1):c.605C>T (p.Pro202Leu)]

NM_000391.4(TPP1):c.605C>T (p.Pro202Leu)

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.605C>T (p.Pro202Leu)
HGVS:
  • NC_000011.10:g.6617057G>A
  • NG_008653.1:g.7405C>T
  • NM_000391.4:c.605C>TMANE SELECT
  • NP_000382.3:p.Pro202Leu
  • LRG_830t1:c.605C>T
  • LRG_830:g.7405C>T
  • LRG_830p1:p.Pro202Leu
  • NC_000011.9:g.6638288G>A
  • NM_000391.3:c.605C>T
  • O14773:p.Pro202Leu
Protein change:
P202L
Links:
UniProtKB: O14773#VAR_063640; UniProtKB/Swiss-Prot: VAR_063640; dbSNP: rs121908205
NCBI 1000 Genomes Browser:
rs121908205
Molecular consequence:
  • NM_000391.4:c.605C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002247008Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 21, 2023) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

New mutations in the neuronal ceroid lipofuscinosis genes.

Mole SE, Zhong NA, Sarpong A, Logan WP, Hofmann S, Yi W, Franken PF, van Diggelen OP, Breuning MH, Moroziewicz D, Ju W, Salonen T, Holmberg V, Järvelä I, Taschner PE.

Eur J Paediatr Neurol. 2001;5 Suppl A:7-10. Review.

PubMed [citation]
PMID:
11589012

Functional consequences and rescue potential of pathogenic missense mutations in tripeptidyl peptidase I.

Walus M, Kida E, Golabek AA.

Hum Mutat. 2010 Jun;31(6):710-21. doi: 10.1002/humu.21251.

PubMed [citation]
PMID:
20340139
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002247008.3

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

Description

This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 202 of the TPP1 protein (p.Pro202Leu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 11589012; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 68747). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TPP1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects TPP1 function (PMID: 20340139). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024