ClinVar Genomic variation as it relates to human health
NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala)
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.
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(19); Uncertain significance(1)
No data submitted for somatic clinical impact
No data submitted for oncogenicity
Variant Details
- Identifiers
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NM_000271.5(NPC1):c.3019C>G (p.Pro1007Ala)
Variation ID: 2966 Accession: VCV000002966.61
- Type and length
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single nucleotide variant, 1 bp
- Location
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Cytogenetic: 18q11.2 18: 23538564 (GRCh38) [ NCBI UCSC ] 18: 21118528 (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 May 3, 2013 Apr 15, 2024 Dec 28, 2023 - HGVS
-
Nucleotide Protein Molecular
consequenceNM_000271.5:c.3019C>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000262.2:p.Pro1007Ala missense NC_000018.10:g.23538564G>C NC_000018.9:g.21118528G>C NG_012795.1:g.53054C>G O15118:p.Pro1007Ala - Protein change
- P1007A
- Other names
- p.P1007A:CCT>GCT
- Canonical SPDI
- NC_000018.10:23538563:G:C
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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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0.00020 (C)
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Allele frequency
Help
The frequency of the allele represented by this VCV record.
Exome Aggregation Consortium (ExAC) 0.00012
The Genome Aggregation Database (gnomAD), exomes 0.00012
Trans-Omics for Precision Medicine (TOPMed) 0.00013
1000 Genomes Project 30x 0.00016
1000 Genomes Project 0.00020
The Genome Aggregation Database (gnomAD) 0.00021
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 | ||
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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. |
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NPC1 | - | - |
GRCh38 GRCh37 |
2442 | 2493 |
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. |
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Conflicting interpretations of pathogenicity (17) |
criteria provided, conflicting classifications
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Dec 28, 2023 | RCV000003100.45 | |
Pathogenic (1) |
criteria provided, single submitter
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Oct 7, 2014 | RCV000415371.4 | |
Pathogenic (6) |
criteria provided, multiple submitters, no conflicts
|
Nov 2, 2021 | RCV000254671.29 | |
Pathogenic (1) |
criteria provided, single submitter
|
Apr 26, 2017 | RCV000321958.4 | |
Pathogenic (1) |
criteria provided, single submitter
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Jan 12, 2021 | RCV002512691.3 | |
Pathogenic (1) |
criteria provided, single submitter
|
Nov 21, 2023 | RCV003952339.1 |
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
(Apr 26, 2017)
|
criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C
Affected status: unknown
Allele origin:
germline
|
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV000696419.1
First in ClinVar: Dec 06, 2016 Last updated: Dec 06, 2016 |
Comment:
Variant summary: The NPC1 c.3019C>G (p.Pro1007Ala) variant involves the alteration of a highly conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this … (more)
Variant summary: The NPC1 c.3019C>G (p.Pro1007Ala) variant involves the alteration of a highly conserved nucleotide. 4/4 in silico tools predict a damaging outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 14/121408 control chromosomes at a frequency of 0.0001153, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). The variant has been reported numerous times in the literature in affected individuals in both the homozygous and compound heterozygous state. Multiple clinical labs classify the variant as pathogenic. Taken together, this variant is classified as pathogenic. (less)
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Pathogenic
(Apr 27, 2017)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
germline
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Illumina Laboratory Services, Illumina
Accession: SCV000407850.3
First in ClinVar: Dec 06, 2016 Last updated: May 24, 2019 |
Comment:
The NPC1 gene is one of two genes in which variants are known to cause Niemann-Pick disease type C. The NPC1 c.3019C>G (p.Pro1007Ala) variant is … (more)
The NPC1 gene is one of two genes in which variants are known to cause Niemann-Pick disease type C. The NPC1 c.3019C>G (p.Pro1007Ala) variant is widely reported as a pathogenic variant and is the second most common pathogenic allele in Western Europe and the US (Patterson et al. 2000). Across a selection of the available literature, the p.Pro1007Ala variant has been identified in at least 44 Niemann-Pick disease type C patients including eight in a homozygous state, 33 in a compound heterozygous state, and three in a heterozygous state (Greer et al. 1999; Ribeiro et al. 2001; Sun et al. 2001; Millat et al. 2001; Bauer et al. 2002; Tarugi et al. 2002; Fernandez-Valero et al. 2005; Jahnova et al. 2014; Pina-Aguilar et al. 2014; Abela et al. 2014; Imrie et al. 2015). The p.Pro1007Ala variant is described as being associated with a variant form of Niemann-Pick disease type C, which presents with a non-classical biochemical profile (Millat et al. 2001; Sun et al. 2001). Control data are unavailable for this variant, which is reported at a frequency of 0.00019 in the European (non-Finnish) population of the Exome Aggregation Consortium. Based on the collective evidence the p.Pro1007Ala variant is classified as pathogenic for Niemann-Pick disease type C. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. (less)
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Pathogenic
(Dec 24, 2019)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
unknown
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Myriad Genetics, Inc.
Accession: SCV001193996.2
First in ClinVar: Apr 06, 2020 Last updated: Jul 03, 2020 |
Comment:
NM_000271.4(NPC1):c.3019C>G(P1007A) is classified as pathogenic in the context of Niemann-Pick disease type C1. Sources cited for classification include the following: PMID 16098014, 11479732 and 11333381. … (more)
NM_000271.4(NPC1):c.3019C>G(P1007A) is classified as pathogenic in the context of Niemann-Pick disease type C1. Sources cited for classification include the following: PMID 16098014, 11479732 and 11333381. Classification of NM_000271.4(NPC1):c.3019C>G(P1007A) is based on the following criteria: This is a well-established pathogenic variant in the literature that has been observed more frequently in patients with clinical diagnoses than in healthy populations. Please note: this variant was assessed in the context of healthy population screening.‚Äã (less)
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Pathogenic
(Oct 23, 2020)
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criteria provided, single submitter
Method: clinical testing
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not provided
(Unknown mechanism)
Affected status: yes
Allele origin:
germline
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Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen
Accession: SCV001447180.1
First in ClinVar: Nov 28, 2020 Last updated: Nov 28, 2020 |
Clinical Features:
Cerebellar ataxia (present)
Sex: female
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Pathogenic
(Apr 07, 2021)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
germline
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Centre for Inherited Metabolic Diseases, Karolinska University Hospital
Accession: SCV001554476.1
First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Number of individuals with the variant: 1
Family history: no
Secondary finding: no
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Pathogenic
(Sep 09, 2022)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
germline
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Laboratorio de Genetica e Diagnostico Molecular, Hospital Israelita Albert Einstein
Accession: SCV003807753.1
First in ClinVar: Mar 04, 2023 Last updated: Mar 04, 2023 |
Comment:
ACMG classification criteria: PS4 strong, PM2 supporting, PM3 very strong, PP1 supporting, PP3 supporting
Number of individuals with the variant: 1
Clinical Features:
Poor suck (present) , Fetal growth restriction (present) , Mild intrauterine growth retardation (present) , Generalized dystonia (present) , Dystonic disorder (present) , Small for … (more)
Poor suck (present) , Fetal growth restriction (present) , Mild intrauterine growth retardation (present) , Generalized dystonia (present) , Dystonic disorder (present) , Small for gestational age (present) , Premature birth (present) , Global developmental delay (present) , Failure to thrive in infancy (present) , Profound global developmental delay (present) , Failure to thrive (present) , Oligohydramnios (present) (less)
Geographic origin: Brazil
Method: Paired-end whole-genome sequencing
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Pathogenic
(Feb 27, 2020)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
germline
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Revvity Omics, Revvity
Accession: SCV002018351.3
First in ClinVar: Nov 29, 2021 Last updated: Feb 04, 2024 |
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Pathogenic
(Dec 28, 2023)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
germline
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Invitae
Accession: SCV000650843.8
First in ClinVar: Dec 26, 2017 Last updated: Feb 20, 2024 |
Comment:
This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1007 of the NPC1 protein (p.Pro1007Ala). … (more)
This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1007 of the NPC1 protein (p.Pro1007Ala). This variant is present in population databases (rs80358257, gnomAD 0.02%). This missense change has been observed in individual(s) with Niemann-Pick type C disease (PMID: 10521290, 11754101, 14639697, 23183285, 23791518, 25425405, 26981555). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 2966). 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 NPC1 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change does not substantially affect NPC1 function (PMID: 15937921). For these reasons, this variant has been classified as Pathogenic. (less)
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Pathogenic
(Nov 21, 2023)
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criteria provided, single submitter
Method: clinical testing
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NPC1-related condition
Affected status: unknown
Allele origin:
germline
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PreventionGenetics, part of Exact Sciences
Accession: SCV004771468.1
First in ClinVar: Mar 16, 2024 Last updated: Mar 16, 2024 |
Comment:
The NPC1 c.3019C>G variant is predicted to result in the amino acid substitution p.Pro1007Ala. This variant has been well-documented as causative for Niemann-Pick disease (see … (more)
The NPC1 c.3019C>G variant is predicted to result in the amino acid substitution p.Pro1007Ala. This variant has been well-documented as causative for Niemann-Pick disease (see for example Greer et al 1999. PubMed ID: 10521290; Bauer et al. 2013. PubMed ID: 23773996; Mavridou et al. 2017. PubMed ID: 28105569; Dardis et al. 2020. PubMed ID: 32138288). Other missense variants, affecting the same amino acid (p.Pro1007Leu, p.Pro1007Arg), have also been reported to be causative for Niemann-Pick disease (Imrie et al. 2015. PubMed ID: 26666848; http://www.hgmd.cf.ac.uk/). This variant is reported in 0.022% of alleles in individuals of European (Non-Finnish) descent in gnomAD. This variant is interpreted as pathogenic. (less)
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Pathogenic
(Mar 01, 2021)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: yes
Allele origin:
germline
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CeGaT Center for Human Genetics Tuebingen
Accession: SCV001249523.20
First in ClinVar: May 12, 2020 Last updated: Apr 15, 2024 |
Number of individuals with the variant: 3
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Pathogenic
(Oct 07, 2014)
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criteria provided, single submitter
Method: clinical testing
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Cerebellar ataxia
Cataplexy Cognitive impairment Headache Postural instability Speech apraxia
Affected status: yes
Allele origin:
unknown
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Centre for Mendelian Genomics, University Medical Centre Ljubljana
Accession: SCV000492760.1
First in ClinVar: Jan 13, 2017 Last updated: Jan 13, 2017 |
|
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Pathogenic
(May 18, 2017)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
unknown
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Fulgent Genetics, Fulgent Genetics
Accession: SCV000611221.1
First in ClinVar: Oct 11, 2015 Last updated: Oct 11, 2015 |
|
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Uncertain significance
(Aug 02, 2017)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000744742.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Dec 04, 2014)
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criteria provided, single submitter
Method: clinical testing
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not provided
Affected status: unknown
Allele origin:
germline
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Eurofins Ntd Llc (ga)
Accession: SCV000227615.5
First in ClinVar: Jun 28, 2015 Last updated: Dec 15, 2018 |
Number of individuals with the variant: 2
Sex: mixed
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Pathogenic
(May 28, 2019)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: unknown
Allele origin:
unknown
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Mendelics
Accession: SCV001140857.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
|
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Pathogenic
(Oct 28, 2018)
|
criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
paternal
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Baylor Genetics
Accession: SCV001528308.1
First in ClinVar: Mar 22, 2021 Last updated: Mar 22, 2021 |
Comment:
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing for Niemann-Pick disease, … (more)
This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease causing for Niemann-Pick disease, type C [PMID 14639697, 23773996, 23791518, 23427322, 26666848] (less)
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Pathogenic
(Mar 05, 2022)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
germline
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DASA
Accession: SCV002107103.2
First in ClinVar: Mar 19, 2022 Last updated: Apr 02, 2022 |
Comment:
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 12955717; 20554533) - PS3_moderate.The c.3019C>G;p.(Pro1007Ala) … (more)
Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 12955717; 20554533) - PS3_moderate.The c.3019C>G;p.(Pro1007Ala) missense variant has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 2966; PMID 14639697; PMID: 23773996; PMID: 23791518; PMID: 23427322; PMID: 26666848) - PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain PM1. The variant is present at low allele frequencies population databases (rs80358257 – gnomAD 0.001167%; ABraOM 0.000427 frequency - http://abraom.ib.usp.br/) - PM2_supporting. The p.(Pro1007Ala) was detected in trans with a pathogenic variant (PMID 14639697; PMID: 23773996; PMID: 23791518) - PM3. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic. (less)
Number of individuals with the variant: 1
Sex: female
Geographic origin: Brazil
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Pathogenic
(Jan 12, 2021)
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criteria provided, single submitter
Method: clinical testing
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Inborn genetic diseases
Affected status: unknown
Allele origin:
germline
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Ambry Genetics
Accession: SCV003556234.1
First in ClinVar: Feb 07, 2023 Last updated: Feb 07, 2023 |
Comment:
The c.3019C>G (p.P1007A) alteration is located in exon 20 (coding exon 20) of the NPC1 gene. This alteration results from a C to G substitution … (more)
The c.3019C>G (p.P1007A) alteration is located in exon 20 (coding exon 20) of the NPC1 gene. This alteration results from a C to G substitution at nucleotide position 3019, causing the proline (P) at amino acid position 1007 to be replaced by an alanine (A). Based on data from the Genome Aggregation Database (gnomAD) database, the NPC1 c.3019C>G alteration was observed in 0.01% (33/282878) of total alleles studied, with a frequency of 0.02% (29/129196) in the European (non-Finnish) subpopulation. This mutation has been identified in numerous homozygous and compound heterozygous individuals with NPC1-related Niemann-Pick disease, many with intermediate or "variant" levels of cholesterol esterification (Millat, 2001; Jahnova, 2014; Reunert, 2016; Musalkova, 2020; Dardis, 2020). The p.P1007A alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic. (less)
Number of individuals with the variant: 1
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Pathogenic
(Nov 02, 2021)
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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: SCV000208910.11
First in ClinVar: Feb 24, 2015 Last updated: Mar 04, 2023 |
Comment:
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: 24676439, … (more)
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: 24676439, 28332184, 32222928, 31980526, 23487299, 24570279, 25131710, 23183285, 28105569, 26981555, 23427322, 26790753, 10521290, 26338816, 24119781, 25236789, 30202070, 28186668, 24915861, 23773996, 23791518, 24386122, 14639697, 11349231, 26666848, 30548255, 16126423, 32138288, 32488064, 33726816) (less)
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Pathogenic
(Jul 24, 2023)
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criteria provided, single submitter
Method: clinical testing
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Niemann-Pick disease, type C1
(Autosomal recessive inheritance)
Affected status: yes
Allele origin:
maternal
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Institute of Human Genetics, University of Leipzig Medical Center
Accession: SCV004027757.1
First in ClinVar: Aug 26, 2023 Last updated: Aug 26, 2023 |
Comment:
Identified as compund heterozygous with NM_000271.5:c.1997G>A. Criteria applied: PM3_VSTR,PM5,PM2_SUP,PP3
Clinical Features:
Splenomegaly (present)
Sex: female
|
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
germline
|
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV000733755.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
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Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001952294.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
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Pathogenic
(Jun 01, 2001)
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no assertion criteria provided
Method: literature only
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NIEMANN-PICK DISEASE, VARIANT TYPE C1
Affected status: not provided
Allele origin:
germline
|
OMIM
Accession: SCV000023258.4
First in ClinVar: Apr 04, 2013 Last updated: Mar 30, 2024 |
Comment on evidence:
For discussion of the pro1007-to-ala (P1007A) mutation in the NPC1 gene that was found in compound heterozygous state in patients with variant Niemann-Pick disease type … (more)
For discussion of the pro1007-to-ala (P1007A) mutation in the NPC1 gene that was found in compound heterozygous state in patients with variant Niemann-Pick disease type C1 (NPC1; 257220) by Sun et al. (2001), see 607623.0011. In 3 families with variant Niemann-Pick disease type C1, Millat et al. (2001) found compound heterozygosity for the 2 most common alleles of the NPC1 gene, I1061T (607623.0010) and P1007A. Compound heterozygosity of these 2 alleles resulted in the juvenile onset of symptoms and a significantly slower progression of the disease than in homozygous I1061T patients. P1007A combined with the nonsense mutation in 1 patient studied by Millat et al. (2001) resulted in the late-infantile neurologic form. (less)
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Likely pathogenic
(Nov 03, 2016)
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no assertion criteria provided
Method: clinical testing
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Niemann-Pick disease, type C1
Affected status: yes
Allele origin:
germline
|
Genome Diagnostics Laboratory, Amsterdam University Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745697.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018 |
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Pathogenic
(Sep 16, 2020)
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no assertion criteria provided
Method: clinical testing
|
Niemann-Pick disease type C1
Affected status: unknown
Allele origin:
germline
|
Natera, Inc.
Accession: SCV001453835.1
First in ClinVar: Jan 02, 2021 Last updated: Jan 02, 2021 |
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Likely pathogenic
(-)
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no assertion criteria provided
Method: clinical testing
|
not provided
Affected status: yes
Allele origin:
germline
|
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Additional submitter:
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen
Study: VKGL Data-share Consensus
Accession: SCV001970102.1 First in ClinVar: Oct 08, 2021 Last updated: Oct 08, 2021 |
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not provided
(-)
|
no classification provided
Method: literature only
|
Niemann-Pick disease, type C1
Affected status: not provided
Allele origin:
unknown
|
GeneReviews
Accession: SCV000040575.3
First in ClinVar: Apr 04, 2013 Last updated: Oct 01, 2022 |
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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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Transcript, protein, metabolite and cellular studies in skin fibroblasts demonstrate variable pathogenic impacts of NPC1 mutations. | Musalkova D | Orphanet journal of rare diseases | 2020 | PMID: 32248828 |
Molecular Genetics of Niemann-Pick Type C Disease in Italy: An Update on 105 Patients and Description of 18 NPC1 Novel Variants. | Dardis A | Journal of clinical medicine | 2020 | PMID: 32138288 |
Niemann-Pick Disease Type C. | Adam MP | - | 2020 | PMID: 20301473 |
Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening. | Reunert J | EBioMedicine | 2015 | PMID: 26981555 |
Observational cohort study of the natural history of Niemann-Pick disease type C in the UK: a 5-year update from the UK clinical database. | Imrie J | BMC neurology | 2015 | PMID: 26666848 |
Early co-occurrence of a neurologic-psychiatric disease pattern in Niemann-Pick type C disease: a retrospective Swiss cohort study. | Abela L | Orphanet journal of rare diseases | 2014 | PMID: 25425405 |
Clinical and genetic characteristics of mexican patients with juvenile presentation of niemann-pick type C disease. | Piña-Aguilar RE | Case reports in neurological medicine | 2014 | PMID: 25349751 |
Observational, retrospective study of a large cohort of patients with Niemann-Pick disease type C in the Czech Republic: a surprisingly stable diagnostic rate spanning almost 40 years. | Jahnova H | Orphanet journal of rare diseases | 2014 | PMID: 25236789 |
Adult form of Niemann-Pick type C with the variant biochemical phenotype on treatment with Miglustat. | Jesús S | Parkinsonism & related disorders | 2013 | PMID: 23791518 |
Genetic screening for Niemann-Pick disease type C in adults with neurological and psychiatric symptoms: findings from the ZOOM study. | Bauer P | Human molecular genetics | 2013 | PMID: 23773996 |
Niemann-Pick type C is frequent in adult ataxia with cognitive decline and vertical gaze palsy. | Schicks J | Neurology | 2013 | PMID: 23427322 |
Teaching video neuroimages: gelastic cataplexy as the first neurologic manifestation of Niemann-Pick disease type C. | Pedroso JL | Neurology | 2012 | PMID: 23183285 |
Exosome secretion ameliorates lysosomal storage of cholesterol in Niemann-Pick type C disease. | Strauss K | The Journal of biological chemistry | 2010 | PMID: 20554533 |
Identification of 25 new mutations in 40 unrelated Spanish Niemann-Pick type C patients: genotype-phenotype correlations. | Fernandez-Valero EM | Clinical genetics | 2005 | PMID: 16098014 |
Niemann-Pick type C disease: subcellular location and functional characterization of NPC2 proteins with naturally occurring missense mutations. | Chikh K | Human mutation | 2005 | PMID: 15937921 |
Adult onset Niemann-Pick type C disease: A clinical, neuroimaging and molecular genetic study. | Battisti C | Movement disorders : official journal of the Movement Disorder Society | 2003 | PMID: 14639697 |
Identification of 58 novel mutations in Niemann-Pick disease type C: correlation with biochemical phenotype and importance of PTC1-like domains in NPC1. | Park WD | Human mutation | 2003 | PMID: 12955717 |
Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts. | Tarugi P | Journal of lipid research | 2002 | PMID: 12401890 |
NPC1: Complete genomic sequence, mutation analysis, and characterization of haplotypes. | Bauer P | Human mutation | 2002 | PMID: 11754101 |
Niemann-Pick type C disease: NPC1 mutations associated with severe and mild cellular cholesterol trafficking alterations. | Ribeiro I | Human genetics | 2001 | PMID: 11479732 |
Niemann-Pick C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1. | Sun X | American journal of human genetics | 2001 | PMID: 11349231 |
Niemann-Pick C1 disease: correlations between NPC1 mutations, levels of NPC1 protein, and phenotypes emphasize the functional significance of the putative sterol-sensing domain and of the cysteine-rich luminal loop. | Millat G | American journal of human genetics | 2001 | PMID: 11333381 |
Mutations in NPC1 highlight a conserved NPC1-specific cysteine-rich domain. | Greer WL | American journal of human genetics | 1999 | PMID: 10521290 |
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=NPC1 | - | - | - | - |
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Text-mined citations for rs80358257 ...
HelpRecord last updated Apr 15, 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.