NM_000310.4(PPT1):c.727-2A>T AND Neuronal ceroid lipofuscinosis 1

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Aug 27, 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:: RCV000049624.6

Allele description [Variation Report for NM_000310.4(PPT1):c.727-2A>T]

NM_000310.4(PPT1):c.727-2A>T

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.727-2A>T

HGVS:

NC_000001.11:g.40076915T>A
NG_009192.1:g.25556A>T
NM_000310.4:c.727-2A>TMANE SELECT
NM_001142604.2:c.418-2A>T
NM_001363695.2:c.726+1645A>T
LRG_690t1:c.727-2A>T
LRG_690:g.25556A>T
NC_000001.10:g.40542587T>A
NM_000310.3:c.727-2A>T

Links:

dbSNP: rs386833664

NCBI 1000 Genomes Browser:

rs386833664

Molecular consequence:

NM_001363695.2:c.726+1645A>T - intron variant - [Sequence Ontology: SO:0001627]
NM_000310.4:c.727-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001142604.2:c.418-2A>T - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000082031	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]
SCV001421942	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 16199547, 10679943, 21990111, 9664077, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000082031

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]

SCV001421942

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 27, 2023)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

Description

FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference: SCV000082031

Help

Summary from all submissions

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

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1).

Salonen T, Järvelä I, Peltonen L, Jalanko A.

Hum Mutat. 2000;15(3):273-9.

PubMed [citation]

PMID:: 10679943

See all PubMed Citations (5)

Details of each submission

From Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM), SCV000082031.1

#	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 Invitae, SCV001421942.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change affects an acceptor splice site in intron 7 of the PPT1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943, 21990111). This variant is present in population databases (rs386833664, gnomAD 0.0009%). Disruption of this splice site has been observed in individual(s) with neuronal ceroid lipofuscinosis (PMID: 9664077). This variant is also known as T (IVS7, -2). ClinVar contains an entry for this variant (Variation ID: 56213). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been 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: Feb 20, 2024

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