NM_000310.4(PPT1):c.541G>T (p.Val181Leu) AND Neuronal ceroid lipofuscinosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 31, 2021
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:: RCV001526944.1

Allele description [Variation Report for NM_000310.4(PPT1):c.541G>T (p.Val181Leu)]

NM_000310.4(PPT1):c.541G>T (p.Val181Leu)

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.541G>T (p.Val181Leu)

HGVS:

NC_000001.11:g.40080483C>A
NG_009192.1:g.21988G>T
NM_000310.4:c.541G>TMANE SELECT
NM_001142604.2:c.232G>T
NM_001363695.2:c.541G>T
NP_000301.1:p.Val181Leu
NP_000301.1:p.Val181Leu
NP_001136076.1:p.Val78Leu
NP_001350624.1:p.Val181Leu
LRG_690t1:c.541G>T
LRG_690:g.21988G>T
LRG_690p1:p.Val181Leu
NC_000001.10:g.40546155C>A
NM_000310.3:c.541G>T
P50897:p.Val181Leu

Protein change:

V181L

Links:

UniProtKB: P50897#VAR_005556; dbSNP: rs148412181

NCBI 1000 Genomes Browser:

rs148412181

Molecular consequence:

NM_000310.4:c.541G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001142604.2:c.232G>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001363695.2:c.541G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Neuronal ceroid lipofuscinosis
Synonyms:: Ceroid storage disease
Identifiers:: MONDO: MONDO:0016295; MedGen: C0027877; Orphanet: 79263; OMIM: PS256730

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001737713	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (May 31, 2021)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 19302939, 28878621, 21499717, 31741823 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001737713

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(May 31, 2021)

germline

clinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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

Citations

PubMed

Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations.

Simonati A, Tessa A, Bernardina BD, Biancheri R, Veneselli E, Tozzi G, Bonsignore M, Grosso S, Piemonte F, Santorelli FM.

Pediatr Neurol. 2009 Apr;40(4):271-6. doi: 10.1016/j.pediatrneurol.2008.10.018.

PubMed [citation]

PMID:: 19302939

The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells.

Pezzini F, Bianchi M, Benfatto S, Griggio F, Doccini S, Carrozzo R, Dapkunas A, Delledonne M, Santorelli FM, Lalowski MM, Simonati A.

Front Mol Neurosci. 2017;10:266. doi: 10.3389/fnmol.2017.00266.

PubMed [citation]

PMID:: 28878621
PMCID:: PMC5572227

See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001737713.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

Variant summary: PPT1 c.541G>T (p.Val181Leu) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.2e-05 in 251372 control chromosomes. c.541G>T has been reported in the literature in multiple individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease) (example, Simonati_2009, Perez-Poyato_2011, Pezzini_2017, Jiliani_2019). These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function. The most pronounced variant effect results in <10% of normal PPT1 enzyme activity (example, Perez-Poyato_2011). Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. 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: Nov 10, 2024

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