NM_000310.4(PPT1):c.871C>T (p.Gln291Ter) AND Neuronal ceroid lipofuscinosis 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: May 2, 2019
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:: RCV000049628.2

Allele description [Variation Report for NM_000310.4(PPT1):c.871C>T (p.Gln291Ter)]

NM_000310.4(PPT1):c.871C>T (p.Gln291Ter)

Gene:

PPT1:palmitoyl-protein thioesterase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_000310.4(PPT1):c.871C>T (p.Gln291Ter)

HGVS:

NC_000001.11:g.40074111G>A
NG_009192.1:g.28360C>T
NM_000310.4:c.871C>TMANE SELECT
NM_001142604.2:c.562C>T
NM_001363695.2:c.799C>T
NP_000301.1:p.Gln291Ter
NP_000301.1:p.Gln291Ter
NP_001136076.1:p.Gln188Ter
NP_001350624.1:p.Gln267Ter
LRG_690t1:c.871C>T
LRG_690:g.28360C>T
LRG_690p1:p.Gln291Ter
NC_000001.10:g.40539783G>A
NM_000310.3:c.871C>T

Protein change:

Q188*

Links:

dbSNP: rs386833668

NCBI 1000 Genomes Browser:

rs386833668

Molecular consequence:

NM_000310.4:c.871C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001142604.2:c.562C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001363695.2:c.799C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis 1 (CLN1)
Synonyms:: CEROID LIPOFUSCINOSIS, NEURONAL, 1, VARIABLE AGE AT ONSET; CLN1 variable age at onset; Infantile CLN (type of CLN1); See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009744; MedGen: C1850451; OMIM: 256730

Recent activity

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cytochrome c oxidase subunit II (mitochondrion) [Aethina tumida]
cytochrome c oxidase subunit II (mitochondrion) [Aethina tumida]
gi|1267174143|ref|YP_009437731.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000082035	Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)	no assertion criteria provided	probable-pathogenic	not provided	not provided	PubMed (1) [See all records that cite this PMID]
SCV001361116	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 2, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000082035

Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)

no assertion criteria provided

probable-pathogenic

not provided

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

SCV001361116

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 2, 2019)

germline

clinical testing

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

Citation Link

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000082035

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Citations

PubMed

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

Identification of three novel mutations of the palmitoyl-protein thioesterase-1 (PPT1) gene in children with neuronal ceroid-lipofuscinosis.

Waliany S, Das AK, Gaben A, Wisniewski KE, Hofmann SL.

Hum Mutat. 2000 Feb;15(2):206-7.

PubMed [citation]

PMID:: 10649502

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082035.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	PubMed (1)

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001361116.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

Variant summary: PPT1 c.871C>T (p.Gln291X) 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. A truncation downstream of this position (p.W296X) has been reported in a patient (PMID: 9664077). The variant was absent in 251410 control chromosomes (gnomAD). c.871C>T has been reported in the literature in a compound heterozygote individual affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease), who had another truncating variant in trans (Waliany 2000). This patient had undetectable enzyme activity, and disease specific electronmicroscopic findings (Waliany 2000). 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 23, 2022

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