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NM_000391.4(TPP1):c.1048C>T (p.Arg350Trp) AND Neuronal ceroid lipofuscinosis

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Jan 12, 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:
RCV003117472.2

Allele description [Variation Report for NM_000391.4(TPP1):c.1048C>T (p.Arg350Trp)]

NM_000391.4(TPP1):c.1048C>T (p.Arg350Trp)

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.1048C>T (p.Arg350Trp)
HGVS:
  • NC_000011.10:g.6616342G>A
  • NG_008653.1:g.8120C>T
  • NM_000391.4:c.1048C>TMANE SELECT
  • NP_000382.3:p.Arg350Trp
  • LRG_830t1:c.1048C>T
  • LRG_830:g.8120C>T
  • LRG_830p1:p.Arg350Trp
  • NC_000011.9:g.6637573G>A
  • NM_000391.3:c.1048C>T
Protein change:
R350W
Links:
dbSNP: rs1554901784
NCBI 1000 Genomes Browser:
rs1554901784
Molecular consequence:
  • NM_000391.4:c.1048C>T - missense variant - [Sequence Ontology: SO:0001583]

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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV003800751Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)
Likely pathogenic
(Jan 12, 2023)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

Neuronal ceroid lipofuscinosis type CLN2: a new rationale for the construction of phenotypic subgroups based on a survey of 25 cases in South America.

Kohan R, Carabelos MN, Xin W, Sims K, Guelbert N, Cismondi IA, Pons P, Alonso GI, Troncoso M, Witting S, Pearce DA, Dodelson de Kremer R, Oller-Ramírez AM, Noher de Halac I.

Gene. 2013 Mar 1;516(1):114-21. doi: 10.1016/j.gene.2012.12.058. Epub 2012 Dec 22.

PubMed [citation]
PMID:
23266810
PMCID:
PMC3855401

Homozygous missense TPP1 mutation associated with mild late infantile neuronal ceroid lipofuscinosis and the genotype-phenotype correlation.

Chen ZR, Liu DT, Meng H, Liu L, Bian WJ, Liu XR, Zhu WW, He Y, Wang J, Tang B, Su T, Yi YH.

Seizure. 2019 Jul;69:180-185. doi: 10.1016/j.seizure.2018.08.027. Epub 2018 Sep 2.

PubMed [citation]
PMID:
31059981
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003800751.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: TPP1 c.1048C>T (p.Arg350Trp) results in a non-conservative amino acid change located in the Peptidase S8/S53 domain (IPR000209) and Sedolisin domain (IPR030400) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251346 control chromosomes. c.1048C>T has been reported in the literature in individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) with co-segregation data providing strong evidence for causality (e.g. Kohan_2013, Chen_2019, Gardner_2019, Lourenco_2020, Guelbert_2022). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) have cited the variant with conflicting assessments; two submitters cite the variant as pathogenic, and two submitters cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely pathogenic.

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

Last Updated: Sep 29, 2024