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NM_000391.4(TPP1):c.380G>A (p.Arg127Gln) AND Neuronal ceroid lipofuscinosis 2

Germline classification:
Likely pathogenic (3 submissions)
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:
RCV000059628.5

Allele description [Variation Report for NM_000391.4(TPP1):c.380G>A (p.Arg127Gln)]

NM_000391.4(TPP1):c.380G>A (p.Arg127Gln)

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.380G>A (p.Arg127Gln)
HGVS:
  • NC_000011.10:g.6617626C>T
  • NG_008653.1:g.6836G>A
  • NM_000391.3:c.[380G>A]
  • NM_000391.4:c.380G>AMANE SELECT
  • NP_000382.3:p.Arg127Gln
  • LRG_830t1:c.380G>A
  • LRG_830:g.6836G>A
  • LRG_830p1:p.Arg127Gln
  • NC_000011.9:g.6638857C>T
  • NM_000391.3:c.380G>A
  • NM_000391.3:c.[380G>A]
  • O14773:p.Arg127Gln
Protein change:
R127Q
Links:
UniProtKB: O14773#VAR_016790; UniProtKB/Swiss-Prot: VAR_016790; dbSNP: rs121908204
NCBI 1000 Genomes Browser:
rs121908204
Molecular consequence:
  • NM_000391.4:c.380G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Neuronal ceroid lipofuscinosis 2
Synonyms:
JANSKY-BIELSCHOWSKY DISEASE NEURONAL CEROID LIPOFUSCINOSIS, LATE INFANTILE; TPP1-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:
MONDO: MONDO:0008769; MedGen: C1876161; Orphanet: 168491; Orphanet: 228349; Orphanet: 79264; OMIM: 204500

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000091195UniProtKB/Swiss-Prot
no classification provided
not providednot providednot provided

PubMed (2)
[See all records that cite these PMIDs]

SCV000793438Counsyl
no assertion criteria provided
Likely pathogenic
(Aug 16, 2017)
unknownclinical testing

PubMed (4)
[See all records that cite these PMIDs]

SCV002072992Neuberg Centre For Genomic Medicine, NCGM
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenicgermlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedunknownunknownnot providednot providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

Citations

PubMed

Heterogeneity of late-infantile neuronal ceroid lipofuscinosis.

Zhong N, Moroziewicz DN, Ju W, Jurkiewicz A, Johnston L, Wisniewski KE, Brown WT.

Genet Med. 2000 Nov-Dec;2(6):312-8.

PubMed [citation]
PMID:
11339651

Late infantile neuronal ceroid lipofuscinosis: quantitative description of the clinical course in patients with CLN2 mutations.

Steinfeld R, Heim P, von Gregory H, Meyer K, Ullrich K, Goebel HH, Kohlschütter A.

Am J Med Genet. 2002 Nov 1;112(4):347-54.

PubMed [citation]
PMID:
12376936
See all PubMed Citations (7)

Details of each submission

From UniProtKB/Swiss-Prot, SCV000091195.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot provided PubMed (2)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From Counsyl, SCV000793438.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Neuberg Centre For Genomic Medicine, NCGM, SCV002072992.1

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

Description

The missense variant p.R127Q in TPP1 (NM_000391.4) has been previously observed in individual(s) with clinical features of neuronal ceroid lipofuscinosis (Zhong et al., 2000; Worgall et al., 2007; Steinfeld et al., 2002). The p.R127Q variant is novel (not in any individuals) in gnomAD Exomes and is novel (not in any individuals) in 1000 Genomes. This variant also falls at the last nucleotide of exon 4 of the TPP1 coding sequence, which is part of the consensus splice site for this exon. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. For these reasons, this variant has been classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024