ClinVar Genomic variation as it relates to human health
NM_000310.4(PPT1):c.490C>T (p.Arg164Ter)
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000310.4(PPT1):c.490C>T (p.Arg164Ter)
Variation ID: 56197 Accession: VCV000056197.15
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 1p34.2 1: 40089456 (GRCh38) [ NCBI UCSC ] 1: 40555128 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
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First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.
Last submission Help The date of the most recent submission for each type of classification for this variant.
Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline Jul 24, 2013 Jul 5, 2025 Dec 19, 2024 - HGVS
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Nucleotide Protein Molecular
consequenceNM_000310.4:c.490C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000301.1:p.Arg164Ter nonsense NM_001142604.2:c.181C>T NP_001136076.1:p.Arg61Ter nonsense NM_001363695.2:c.490C>T NP_001350624.1:p.Arg164Ter nonsense NC_000001.11:g.40089456G>A NC_000001.10:g.40555128G>A NG_009192.1:g.13015C>T LRG_690:g.13015C>T LRG_690t1:c.490C>T LRG_690p1:p.Arg164Ter - Protein change
- R164*, R61*
- Other names
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NM_000310.4(PPT1):c.490C>T
p.Arg164Ter
- Canonical SPDI
- NC_000001.11:40089455:G:A
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Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
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Global minor allele
frequency (GMAF) HelpThe global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.
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Allele frequency
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The frequency of the allele represented by this VCV record.
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Trans-Omics for Precision Medicine (TOPMed) 0.00001
Exome Aggregation Consortium (ExAC) 0.00002
The Genome Aggregation Database (gnomAD), exomes 0.00001
- Links
Genes
Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
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Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
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HI score
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The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
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The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
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The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
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The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene. |
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PPT1 | Gene associated with autosomal recessive phenotype | No evidence available |
GRCh38 GRCh37 |
721 | 751 |
Conditions - Germline
Condition
Help
The condition for this variant-condition (RCV) record in ClinVar. |
Classification
Help
The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions) |
Review status
Help
The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. |
Last evaluated
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The most recent date that a submitter evaluated this variant for the condition. |
Variation/condition record
Help
The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page. |
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Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
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Dec 19, 2024 | RCV000049608.18 | |
Pathogenic (1) |
criteria provided, single submitter
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Aug 15, 2023 | RCV004700345.1 |
Submissions - Germline
Classification
Help
The submitted germline classification for each SCV record. (Last evaluated) |
Review status
Help
Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria) |
Condition
Help
The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant. |
Submitter
Help
The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar. |
More information
Help
This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter. |
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Pathogenic
(Oct 05, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
unknown
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Baylor Genetics
Accession: SCV004204133.1
First in ClinVar: Dec 30, 2023 Last updated: Dec 30, 2023 |
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Pathogenic
(Aug 15, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
Method: clinical testing
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Not Provided
Affected status: yes
Allele origin:
germline
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GeneDx
Accession: SCV005201782.1
First in ClinVar: Sep 16, 2024 Last updated: Sep 16, 2024 |
Comment:
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of … (more)
Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 28367323, 21990111, 21704547, 24997880, 10649502, 31741823, 9664077) (less)
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Pathogenic
(Jan 25, 2023)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: curation
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Neuronal ceroid lipofuscinosis 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
germline
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Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV003761274.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The homozygous p.Arg164Ter variant in PPT1 was identified by our study in two siblings with neuronal ceroid lipofuscinosis. The p.Arg164Ter variant in PPT1 has been … (more)
The homozygous p.Arg164Ter variant in PPT1 was identified by our study in two siblings with neuronal ceroid lipofuscinosis. The p.Arg164Ter variant in PPT1 has been previously reported in four unrelated individuals with neuronal ceroid lipofuscinosis 1 (PMID: 31741823, PMID: 21990111, PMID: 10649502, PMID: 9664077), but has been identified in 0.005% (1/18394) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs386833649). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Of the four affected individuals previously reported (PMID: 31741823, PMID: 21990111, PMID: 10649502, PMID: 9664077), three were compound heterozygotes who carried pathogenic or likely pathogenic variants in trans (PMID: 31741823, PMID: 21990111, PMID: 9664077, ClinVar Variation ID: 8904), and one was a compound heterozygote who carried a variant of uncertain significance in trans (PMID: 10649502, ClinVar Variation ID: 56217), and the affected siblings identified by our study were homozygotes, which increases the likelihood that the p.Arg164Ter variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 56197) and has been interpreted as pathogenic by Invitae and the Shahid Beheshti University of Medical Sciences Genomic Research Center and as likely pathogenic by Counsyl. This nonsense variant leads to a premature termination codon at position 164, which is predicted to lead to a truncated or absent protein. Loss of function of the PPT1 gene is an established mechanism of autosomal recessive neuronal ceroid lipofuscinosis 1. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive neuronal ceroid lipofuscinosis 1. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3_Strong (Richards 2015). (less)
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Pathogenic
(Dec 19, 2024)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
germline
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Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001590137.5
First in ClinVar: May 10, 2021 Last updated: Feb 25, 2025 |
Comment:
This sequence change creates a premature translational stop signal (p.Arg164*) in the PPT1 gene. It is expected to result in an absent or disrupted protein … (more)
This sequence change creates a premature translational stop signal (p.Arg164*) in the PPT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PPT1 are known to be pathogenic (PMID: 10679943, 21990111). This variant is present in population databases (rs386833649, gnomAD 0.006%). This premature translational stop signal has been observed in individuals with neuronal ceroid lipofuscinosis (PMID: 9664077, 10649502). ClinVar contains an entry for this variant (Variation ID: 56197). 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. (less)
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Pathogenic
(Dec 18, 2017)
C
Contributing to aggregate classification
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criteria provided, single submitter
Method: clinical testing
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Neuronal ceroid lipofuscinosis 1
Affected status: yes
Allele origin:
inherited
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Genomic Research Center, Shahid Beheshti University of Medical Sciences
Accession: SCV000746400.3
First in ClinVar: Mar 29, 2015 Last updated: Apr 13, 2025 |
Age: 10-19 years
Sex: female
Geographic origin: Iran
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Likely pathogenic
(-)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: not provided
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Ceroid lipofuscinosis neuronal 1
Affected status: not provided
Allele origin:
unknown
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Juha Muilu Group; Institute for Molecular Medicine Finland (FIMM)
Accession: SCV000082015.2
First in ClinVar: Jul 24, 2013 Last updated: Jun 08, 2025
Comment:
FinDis database variant: This variant was not found or characterized by our laboratory, data were collected from public sources: see reference
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Comment:
Converted during submission from probable-pathogenic to Likely pathogenic.
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Likely pathogenic
(Aug 26, 2014)
N
Not contributing to aggregate classification
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no assertion criteria provided
Method: literature only
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Ceroid lipofuscinosis neuronal 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
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Counsyl
Accession: SCV000220640.3
First in ClinVar: Mar 29, 2015 Last updated: Jul 05, 2025 |
Comment:
This submission and the accompanying classification are no longer maintained by the submitter. For more information on current observations and classification, please contact variantquestions@myriad.com.
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Germline Functional Evidence
There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar. |
Citations for germline classification of this variant
HelpTitle | Author | Journal | Year | Link |
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Update of the mutation spectrum and clinical correlations of over 360 mutations in eight genes that underlie the neuronal ceroid lipofuscinoses. | Kousi M | Human mutation | 2012 | PMID: 21990111 |
Neuronal ceroid lipofuscinoses: research update. | Wisniewski KE | Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology | 2000 | PMID: 11073228 |
Detection of eight novel palmitoyl protein thioesterase (PPT) mutations underlying infantile neuronal ceroid lipofuscinosis (INCL;CLN1). | Salonen T | Human mutation | 2000 | PMID: 10679943 |
Identification of three novel mutations of the palmitoyl-protein thioesterase-1 (PPT1) gene in children with neuronal ceroid-lipofuscinosis. | Waliany S | Human mutation | 2000 | PMID: 10649502 |
Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S. | Das AK | The Journal of clinical investigation | 1998 | PMID: 9664077 |
Text-mined citations for rs386833649 ...
HelpRecord last updated Jul 05, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.