NM_000391.4(TPP1):c.1016G>A (p.Arg339Gln) AND Ceroid lipofuscinosis neuronal 2

Clinical significance:Likely pathogenic (Last evaluated: May 18, 2021)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
4 submissions [Details]
Record status:
current
Accession:
RCV000625040.4

Allele description [Variation Report for NM_000391.4(TPP1):c.1016G>A (p.Arg339Gln)]

NM_000391.4(TPP1):c.1016G>A (p.Arg339Gln)

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.1016G>A (p.Arg339Gln)
HGVS:
  • NC_000011.10:g.6616374C>T
  • NG_008653.1:g.8088G>A
  • NM_000391.4:c.1016G>AMANE SELECT
  • NP_000382.3:p.Arg339Gln
  • LRG_830t1:c.1016G>A
  • LRG_830:g.8088G>A
  • LRG_830p1:p.Arg339Gln
  • NC_000011.9:g.6637605C>T
  • NM_000391.3:c.1016G>A
  • O14773:p.Arg339Gln
Protein change:
R339Q
Links:
UniProtKB: O14773#VAR_066886; dbSNP: rs765380155
NCBI 1000 Genomes Browser:
rs765380155
Molecular consequence:
  • NM_000391.4:c.1016G>A - missense variant - [Sequence Ontology: SO:0001583]
Functional consequence:
variation affecting protein [Variation Ontology: 0002]

Condition(s)

Name:
Ceroid lipofuscinosis neuronal 2 (CLN2)
Synonyms:
TPP1-Related Neuronal Ceroid-Lipofuscinosis
Identifiers:
MONDO: MONDO:0008769; MedGen: C1876161; Orphanet: 168491; Orphanet: 228349; Orphanet: 79264; OMIM: 204500

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000743598Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensuscriteria provided, single submitter
Likely pathogenic
(Jul 28, 2017)
germlineclinical testing

Citation Link,

SCV000744908Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensuscriteria provided, single submitter
Likely pathogenic
(Jun 17, 2016)
germlineclinical testing

Citation Link,

SCV001737219Nilou-Genome Labcriteria provided, single submitter
Likely pathogenic
(May 18, 2021)
germlineclinical testing

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

SCV001762275Human Genetics Research Group,Shri Mata Vaishno Devi Universityno assertion criteria providedPathogenic
(Jul 29, 2021)
germlineresearch

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
Jammu and Kashmir Hindugermlineyes1not providednot providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Genome Diagnostics Laboratory, University Medical Center Utrecht - VKGL Data-share Consensus, SCV000743598.1

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

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV000744908.1

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

From Nilou-Genome Lab, SCV001737219.1

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

From Human Genetics Research Group,Shri Mata Vaishno Devi University, SCV001762275.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Jammu and Kashmir Hindu1not providednot providedresearchnot provided

Description

Variant segregating with disease in family in autosomal recessive manner where unaffected parents were found heterozygous whereas, affected patient was found Homozygous for the variation. The Patient also has shown pathologically low enzymatic activity of TPP1 in the blood sample (<0.49 μmol/L/h; pathological reference = <0.5 μmol/L/h).

Description

We confirmed the missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene, segregating with disease in family and in silico analyses predicted the variant to be highly pathogenic that corelated with pathologically low enzymatic activity of TPP1 in the proband's blood sample (<0.49 μmol/L/h; pathological reference = <0.5 μmol/L/h). Reference source OMIM: 204500 Neuronal ceroid lipofuscinosis-2 is caused by homozygous or compound heterozygous mutation in the TPP1 gene (607998) on chromosome 11p15. Reference source ClinVar: RCV000699225.1 NM_000391.4(TPP1):c.1016G>A (p.Arg339Gln) and Neuronal ceroid lipofuscinosis https://www.ncbi.nlm.nih.gov/clinvar/RCV000699225.1/

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot provided1not providednot providednot provided

Last Updated: Sep 23, 2021

Support Center