NM_000391.4(TPP1):c.887-10A>G AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Pathogenic(1);Uncertain significance(1) (Last evaluated: Aug 23, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000359791.2

Allele description [Variation Report for NM_000391.4(TPP1):c.887-10A>G]

NM_000391.4(TPP1):c.887-10A>G

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.887-10A>G
HGVS:
  • NC_000011.10:g.6616513T>C
  • NG_008653.1:g.7949A>G
  • NM_000391.4:c.887-10A>GMANE SELECT
  • LRG_830t1:c.887-10A>G
  • LRG_830:g.7949A>G
  • NC_000011.9:g.6637744T>C
  • NM_000391.3:c.887-10A>G
Note:
NCBI staff reviewed the sequence information reported in PubMed 17959406 Fig. 2 to determine the location of this allele on the current reference sequence.
Nucleotide change:
IVS7AS, A-G, -10
Links:
OMIM: 607998.0009; dbSNP: rs755445790
NCBI 1000 Genomes Browser:
rs755445790
Molecular consequence:
  • NM_000391.4:c.887-10A>G - intron variant - [Sequence Ontology: SO:0001627]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000344872EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Sep 15, 2016)
germlineclinical testing

Citation Link,

SCV001394610Invitaecriteria provided, single submitter
Pathogenic
(Aug 23, 2020)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not 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

CLN2/TPP1 deficiency: the novel mutation IVS7-10A>G causes intron retention and is associated with a mild disease phenotype.

Bessa C, Teixeira CA, Dias A, Alves M, Rocha S, Lacerda L, Loureiro L, Guimarães A, Ribeiro MG.

Mol Genet Metab. 2008 Jan;93(1):66-73. Epub 2007 Oct 23.

PubMed [citation]
PMID:
17959406
See all PubMed Citations (3)

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000344872.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From Invitae, SCV001394610.2

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

Description

This sequence change falls in intron 7 of the TPP1 gene. It does not directly change the encoded amino acid sequence of the TPP1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed to segregate with neuronal ceroid lipofuscinosis in a family, and has also been observed in unrelated affected individuals (PMID: 17959406, 23266810). It is also known as IVS7-10A>G in the literature. ClinVar contains an entry for this variant (Variation ID: 2649). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 17959406). 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: May 10, 2021

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