Variant summary: PPT1 c.541G>A (p.Val181Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.7e-05 in 277014 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PPT1 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) (8.7e-05 vs 0.00073), allowing no conclusion about variant significance. c.541G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease, Das_1998, Santorelli_2013, Poyato_2012). 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 enzyme activity. The most pronounced variant effect results in <10% of normal activity (Das_1998, Poyato_2012). 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.
ClinVar Genomic variation as it relates to human health
NM_000310.4(PPT1):c.541G>A (p.Val181Met)
Germline
Classification
Help
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.
(11)
Help
Stars represent the aggregate review status, or the level of review supporting the aggregate germline classification for this VCV record. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status. The number of submissions which contribute to this review status is shown in parentheses.
Pathogenic/Likely pathogenic
11
criteria provided, multiple submitters, no conflicts
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000310.4(PPT1):c.541G>A (p.Val181Met)
Variation ID: 188857 Accession: VCV000188857.24
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p34.2 1: 40080483 (GRCh38) [ NCBI UCSC ] 1: 40546155 (GRCh37) [ NCBI UCSC ]
- Timeline in ClinVar
-
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 Mar 29, 2015 Jun 17, 2024 Mar 10, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000310.4:c.541G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000301.1:p.Val181Met missense NM_001142604.2:c.232G>A NP_001136076.1:p.Val78Met missense NM_001363695.2:c.541G>A NP_001350624.1:p.Val181Met missense NC_000001.11:g.40080483C>T NC_000001.10:g.40546155C>T NG_009192.1:g.21988G>A LRG_690:g.21988G>A LRG_690t1:c.541G>A LRG_690p1:p.Val181Met P50897:p.Val181Met - Protein change
- V181M, V78M
- Other names
- -
- Canonical SPDI
- NC_000001.11:40080482:C:T
-
Functional
consequence HelpThe effect of the variant on RNA or protein function, based on experimental evidence from submitters.
- -
-
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.
- -
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
Trans-Omics for Precision Medicine (TOPMed) 0.00003
The Genome Aggregation Database (gnomAD) 0.00006
NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008
- Links
Genes
| Gene | OMIM | ClinGen Gene Dosage Sensitivity Curation |
Variation Viewer
Help
Links to Variation Viewer, a genome browser to view variation data from NCBI databases. |
Related variants | ||
|---|---|---|---|---|---|---|
| HI score
Help
The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
TS score
Help
The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team. |
Within gene
Help
The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants. |
All
Help
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. |
|||
| PPT1 | - | - |
GRCh38 GRCh37 |
695 | 723 | |
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
Help
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. |
|---|---|---|---|---|
| Pathogenic/Likely pathogenic (8) |
criteria provided, multiple submitters, no conflicts
|
Mar 10, 2024 | RCV000169209.21 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Apr 1, 2021 | RCV001723740.3 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jun 22, 2022 | RCV002259317.2 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Jul 19, 2019 | RCV002345567.2 |
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. |
|
|---|---|---|---|---|---|
|
Likely pathogenic
(Jun 27, 2014)
|
criteria provided, single submitter
Method: literature only
|
Ceroid lipofuscinosis neuronal 1
(Autosomal recessive inheritance)
Affected status: unknown
Allele origin:
unknown
|
Counsyl
Accession: SCV000220464.2
First in ClinVar: Mar 29, 2015 Last updated: Dec 24, 2022 |
|
|
|
Pathogenic
(Jan 04, 2016)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: yes
Allele origin:
inherited
|
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne
Accession: SCV000965817.1
First in ClinVar: Aug 26, 2019 Last updated: Aug 26, 2019 |
|
|
|
Pathogenic
(Mar 11, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361117.1
First in ClinVar: Jun 22, 2020 Last updated: Jun 22, 2020 |
Comment:
Variant summary: PPT1 c.541G>A (p.Val181Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging … (more)
Variant summary: PPT1 c.541G>A (p.Val181Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.7e-05 in 277014 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PPT1 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) (8.7e-05 vs 0.00073), allowing no conclusion about variant significance. c.541G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease, Das_1998, Santorelli_2013, Poyato_2012). 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 enzyme activity. The most pronounced variant effect results in <10% of normal activity (Das_1998, Poyato_2012). 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. (less)
|
|
|
Pathogenic
(Apr 12, 2021)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Centre for Inherited Metabolic Diseases, Karolinska University Hospital
Accession: SCV001571358.1
First in ClinVar: Apr 18, 2021 Last updated: Apr 18, 2021 |
Family history: no
Secondary finding: no
|
|
|
Pathogenic
(Apr 01, 2021)
|
criteria provided, single submitter
Method: curation
|
Retinitis pigmentosa
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
|
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard
Accession: SCV001950330.1
First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Comment:
The p.Val181Met variant in PPT1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics … (more)
The p.Val181Met variant in PPT1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3, PS3, PP1-M, PM1. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab. (less)
|
|
|
Pathogenic
(Jun 22, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Not Provided
Affected status: yes
Allele origin:
germline
|
GeneDx
Accession: SCV002538723.2
First in ClinVar: Jul 01, 2022 Last updated: Mar 04, 2023 |
Comment:
Published functional studies demonstrate that V181M results in almost complete loss of wild-type function (Das et al., 2001); Located in the palmitate-binding site and it … (more)
Published functional studies demonstrate that V181M results in almost complete loss of wild-type function (Das et al., 2001); Located in the palmitate-binding site and it is hypothesized that the V181M substitution alters the active site pocket (Ohno et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15464427, 12796825, 12125808, 28878621, 11073228, 11589007, 21990111, 21499717, 24091420, 15965709, 10649502, 31589614, 30541466, 33726816, 23374165, 33849402, 22387303, 11440996, 19793631, 9664077) (less)
|
|
|
Pathogenic
(Mar 14, 2022)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
germline
|
Revvity Omics, Revvity
Accession: SCV003826627.2
First in ClinVar: Mar 04, 2023 Last updated: Feb 04, 2024 |
|
|
|
Pathogenic
(Jan 29, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
germline
|
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV000958226.6
First in ClinVar: Aug 14, 2019 Last updated: Feb 28, 2024 |
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 181 of the PPT1 protein (p.Val181Met). … (more)
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 181 of the PPT1 protein (p.Val181Met). This variant is present in population databases (rs148412181, gnomAD 0.02%). This missense change has been observed in individuals with neuronal ceroid lipofucinosis (NCL) (PMID: 9664077, 10191107, 10649502, 15464427, 19302939, 22387303, 23374165, 30541466). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 188857). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PPT1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PPT1 function (PMID: 9664077, 11440996, 28878621). This variant disrupts the p.Val181 amino acid residue in PPT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19302939, 21499717). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. (less)
|
|
|
Pathogenic
(Jul 19, 2019)
|
criteria provided, single submitter
Method: clinical testing
|
Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
|
Ambry Genetics
Accession: SCV002649347.2
First in ClinVar: Nov 29, 2022 Last updated: May 01, 2024 |
Comment:
The p.V181M pathogenic mutation (also known as c.541G>A), located in coding exon 6 of the PPT1 gene, results from a G to A substitution at … (more)
The p.V181M pathogenic mutation (also known as c.541G>A), located in coding exon 6 of the PPT1 gene, results from a G to A substitution at nucleotide position 541. The valine at codon 181 is replaced by methionine, an amino acid with highly similar properties. This mutation has been identified in multiple individuals with neuronal ceroid lipofuscinosis, including in the homozygous state in 3 individuals from 2 families (Das AK et al. J. Clin. Invest., 1998 Jul;102:361-70; Waliany S et al. Hum. Mutat., 2000 Feb;15:206-7; Mole SE et al. Hum. Mutat., 1999;14:199-215; Teixeira C et al. J. Neurol., 2003 Jun;250:661-7; Pérez Poyato MS et al. Gene, 2012 May;499:297-302; Santorelli FM et al. Orphanet J Rare Dis, 2013 Feb;8:19; Sheth J et al. BMC Neurol, 2018 Dec;18:203). Analysis of this mutation in SF9 cells as well as patient derived lymphoblasts showed o detectable palmitoyl-protein thioesterase activity (Das AK et al. Hum. Mol. Genet., 2001 Jun;10:1431-9). Another study suggested abnormal processing of protein containing this mutation (Pezzini F et al. Front Mol Neurosci, 2017 Aug;10:266). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation. (less)
|
|
|
Pathogenic
(Mar 10, 2024)
|
criteria provided, single submitter
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
unknown
|
Baylor Genetics
Accession: SCV004204132.2
First in ClinVar: Dec 30, 2023 Last updated: Jun 17, 2024 |
|
|
|
Pathogenic
(Jun 07, 2021)
|
no assertion criteria provided
Method: clinical testing
|
Neuronal ceroid lipofuscinosis 1
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV002085986.1
First in ClinVar: Apr 23, 2022 Last updated: Apr 23, 2022 |
|
|
| click to load more click to collapse | |||||
Comment:
Comment:
The p.Val181Met variant in PPT1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3, PS3, PP1-M, PM1. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Comment:
Published functional studies demonstrate that V181M results in almost complete loss of wild-type function (Das et al., 2001); Located in the palmitate-binding site and it is hypothesized that the V181M substitution alters the active site pocket (Ohno et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15464427, 12796825, 12125808, 28878621, 11073228, 11589007, 21990111, 21499717, 24091420, 15965709, 10649502, 31589614, 30541466, 33726816, 23374165, 33849402, 22387303, 11440996, 19793631, 9664077)
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 181 of the PPT1 protein (p.Val181Met). This variant is present in population databases (rs148412181, gnomAD 0.02%). This missense change has been observed in individuals with neuronal ceroid lipofucinosis (NCL) (PMID: 9664077, 10191107, 10649502, 15464427, 19302939, 22387303, 23374165, 30541466). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 188857). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PPT1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PPT1 function (PMID: 9664077, 11440996, 28878621). This variant disrupts the p.Val181 amino acid residue in PPT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19302939, 21499717). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.V181M pathogenic mutation (also known as c.541G>A), located in coding exon 6 of the PPT1 gene, results from a G to A substitution at nucleotide position 541. The valine at codon 181 is replaced by methionine, an amino acid with highly similar properties. This mutation has been identified in multiple individuals with neuronal ceroid lipofuscinosis, including in the homozygous state in 3 individuals from 2 families (Das AK et al. J. Clin. Invest., 1998 Jul;102:361-70; Waliany S et al. Hum. Mutat., 2000 Feb;15:206-7; Mole SE et al. Hum. Mutat., 1999;14:199-215; Teixeira C et al. J. Neurol., 2003 Jun;250:661-7; Pérez Poyato MS et al. Gene, 2012 May;499:297-302; Santorelli FM et al. Orphanet J Rare Dis, 2013 Feb;8:19; Sheth J et al. BMC Neurol, 2018 Dec;18:203). Analysis of this mutation in SF9 cells as well as patient derived lymphoblasts showed o detectable palmitoyl-protein thioesterase activity (Das AK et al. Hum. Mol. Genet., 2001 Jun;10:1431-9). Another study suggested abnormal processing of protein containing this mutation (Pezzini F et al. Front Mol Neurosci, 2017 Aug;10:266). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
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. |
Comment:
Variant summary: PPT1 c.541G>A (p.Val181Met) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 8.7e-05 in 277014 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in PPT1 causing Neuronal Ceroid-Lipofuscinosis (Batten Disease) (8.7e-05 vs 0.00073), allowing no conclusion about variant significance. c.541G>A has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Neuronal Ceroid-Lipofuscinosis (Batten Disease, Das_1998, Santorelli_2013, Poyato_2012). 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 enzyme activity. The most pronounced variant effect results in <10% of normal activity (Das_1998, Poyato_2012). 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.
Comment:
The p.Val181Met variant in PPT1 was identified in an individual with Retinitis pigmentosa, via a collaborative study between the Broad Institute's Center for Mendelian Genomics and the Pierce lab (https://oculargenomics.meei.harvard.edu/labs/pierce-lab/lab-members/). Through a review of available evidence we were able to apply the following criteria: PM2, PP3, PM3, PS3, PP1-M, PM1. Based on this evidence we have classified this variant as Pathogenic. If you have any questions about the classification please reach out to the Pierce Lab.
Comment:
Published functional studies demonstrate that V181M results in almost complete loss of wild-type function (Das et al., 2001); Located in the palmitate-binding site and it is hypothesized that the V181M substitution alters the active site pocket (Ohno et al., 2010); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 15464427, 12796825, 12125808, 28878621, 11073228, 11589007, 21990111, 21499717, 24091420, 15965709, 10649502, 31589614, 30541466, 33726816, 23374165, 33849402, 22387303, 11440996, 19793631, 9664077)
Comment:
This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 181 of the PPT1 protein (p.Val181Met). This variant is present in population databases (rs148412181, gnomAD 0.02%). This missense change has been observed in individuals with neuronal ceroid lipofucinosis (NCL) (PMID: 9664077, 10191107, 10649502, 15464427, 19302939, 22387303, 23374165, 30541466). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 188857). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PPT1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects PPT1 function (PMID: 9664077, 11440996, 28878621). This variant disrupts the p.Val181 amino acid residue in PPT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19302939, 21499717). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Comment:
The p.V181M pathogenic mutation (also known as c.541G>A), located in coding exon 6 of the PPT1 gene, results from a G to A substitution at nucleotide position 541. The valine at codon 181 is replaced by methionine, an amino acid with highly similar properties. This mutation has been identified in multiple individuals with neuronal ceroid lipofuscinosis, including in the homozygous state in 3 individuals from 2 families (Das AK et al. J. Clin. Invest., 1998 Jul;102:361-70; Waliany S et al. Hum. Mutat., 2000 Feb;15:206-7; Mole SE et al. Hum. Mutat., 1999;14:199-215; Teixeira C et al. J. Neurol., 2003 Jun;250:661-7; Pérez Poyato MS et al. Gene, 2012 May;499:297-302; Santorelli FM et al. Orphanet J Rare Dis, 2013 Feb;8:19; Sheth J et al. BMC Neurol, 2018 Dec;18:203). Analysis of this mutation in SF9 cells as well as patient derived lymphoblasts showed o detectable palmitoyl-protein thioesterase activity (Das AK et al. Hum. Mol. Genet., 2001 Jun;10:1431-9). Another study suggested abnormal processing of protein containing this mutation (Pezzini F et al. Front Mol Neurosci, 2017 Aug;10:266). Based on the supporting evidence, this alteration is interpreted as a disease-causing mutation.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| The importance of automation in genetic diagnosis: Lessons from analyzing an inherited retinal degeneration cohort with the Mendelian Analysis Toolkit (MATK). | Zampaglione E | Genetics in medicine : official journal of the American College of Medical Genetics | 2022 | PMID: 34906470 |
| Batten disease: biochemical and molecular characterization revealing novel PPT1 and TPP1 gene mutations in Indian patients. | Sheth J | BMC neurology | 2018 | PMID: 30541466 |
| The Networks of Genes Encoding Palmitoylated Proteins in Axonal and Synaptic Compartments Are Affected in PPT1 Overexpressing Neuronal-Like Cells. | Pezzini F | Frontiers in molecular neuroscience | 2017 | PMID: 28878621 |
| Molecular epidemiology of childhood neuronal ceroid-lipofuscinosis in Italy. | Santorelli FM | Orphanet journal of rare diseases | 2013 | PMID: 23374165 |
| Infantile neuronal ceroid lipofuscinosis: follow-up on a Spanish series. | Pérez Poyato MS | Gene | 2012 | PMID: 22387303 |
| Juvenile neuronal ceroid lipofuscinosis: clinical course and genetic studies in Spanish patients. | Pérez-Poyato MS | Journal of inherited metabolic disease | 2011 | PMID: 21499717 |
| Variant late infantile neuronal ceroid lipofuscinosis because of CLN1 mutations. | Simonati A | Pediatric neurology | 2009 | PMID: 19302939 |
| Electroretinographic and clinicopathologic correlations of retinal dysfunction in infantile neuronal ceroid lipofuscinosis (infantile Batten disease). | Weleber RG | Molecular genetics and metabolism | 2004 | PMID: 15464427 |
| Clinicopathological and molecular characterization of neuronal ceroid lipofuscinosis in the Portuguese population. | Teixeira C | Journal of neurology | 2003 | PMID: 12796825 |
| Biochemical analysis of mutations in palmitoyl-protein thioesterase causing infantile and late-onset forms of neuronal ceroid lipofuscinosis. | Das AK | Human molecular genetics | 2001 | PMID: 11440996 |
| 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 |
| 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 basis of the neuronal ceroid lipofuscinoses: mutations in CLN1, CLN2, CLN3, and CLN5. | Mole SE | Human mutation | 1999 | PMID: 10477428 |
| Genotype-phenotype correlations in neuronal ceroid lipofuscinosis due to palmitoyl-protein thioesterase deficiency. | Hofmann SL | Molecular genetics and metabolism | 1999 | PMID: 10191107 |
| Molecular genetics of palmitoyl-protein thioesterase deficiency in the U.S. | Das AK | The Journal of clinical investigation | 1998 | PMID: 9664077 |
| click to load more click to collapse | ||||
Text-mined citations for rs148412181 ...
HelpThese citations are identified by LitVar using
the rs number, so they may include citations for more than one variant
at this location. Please review the LitVar results carefully for your
variant of interest.
Record last updated Sep 29, 2024
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.