NM_000391.4(TPP1):c.972_979del (p.Ser324fs) AND Ceroid lipofuscinosis neuronal 2

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Mar 20, 2020)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000169200.2

Allele description [Variation Report for NM_000391.4(TPP1):c.972_979del (p.Ser324fs)]

NM_000391.4(TPP1):c.972_979del (p.Ser324fs)

Gene:
TPP1:tripeptidyl peptidase 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p15.4
Genomic location:
Preferred name:
NM_000391.4(TPP1):c.972_979del (p.Ser324fs)
HGVS:
  • NC_000011.10:g.6616414_6616421del
  • NG_008653.1:g.8044_8051del
  • NM_000391.4:c.972_979delMANE SELECT
  • NP_000382.3:p.Ser324fs
  • LRG_830t1:c.972_979del
  • LRG_830:g.8044_8051del
  • LRG_830p1:p.Ser324fs
  • NC_000011.9:g.6637645_6637652del
  • NM_000391.3:c.972_979del8
  • NM_000391.3:c.972_979delCTATGGAG
Protein change:
S324fs
Links:
dbSNP: rs778232650
NCBI 1000 Genomes Browser:
rs778232650
Molecular consequence:
  • NM_000391.4:c.972_979del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000220449Counsylcriteria provided, single submitter
Likely pathogenic
(Jun 23, 2014)
unknownliterature only

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

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV001339059Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Mar 20, 2020)
germlineclinical testing

PubMed (6)
[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
not providedunknownunknownnot providednot providednot providednot providednot providedliterature only

Citations

PubMed

Molecular basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5.

Mole SE, Mitchison HM, Munroe PB.

Hum Mutat. 1999;14(3):199-215. Review.

PubMed [citation]
PMID:
10477428

Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses.

Kousi M, Lehesjoki AE, Mole SE.

Hum Mutat. 2012 Jan;33(1):42-63. doi: 10.1002/humu.21624. Epub 2011 Nov 16. Review.

PubMed [citation]
PMID:
21990111
See all PubMed Citations (6)

Details of each submission

From Counsyl, SCV000220449.1

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339059.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

Variant summary: TPP1 c.972_979delCTATGGAG (p.Ser324ArgfsX2) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 4e-06 in 251378 control chromosomes (gnomAD). c.972_979delCTATGGAG has been reported in the literature in individuals affected with Late-infantile Neuronal Ceroid-Lipofuscinoses (Sleat_1999). These data indicate that the variant may be associated with disease. At least one publication reports this variant has an impact on protein function and results in <10% of normal TPP1 activity. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.

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

Last Updated: Nov 27, 2021

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