NM_000271.5(NPC1):c.2683dup (p.Glu895fs) AND Niemann-Pick disease, type C1

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: Jul 8, 2022
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000666985.4

Allele description [Variation Report for NM_000271.5(NPC1):c.2683dup (p.Glu895fs)]

NM_000271.5(NPC1):c.2683dup (p.Glu895fs)

Gene:

NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

18q11.2

Genomic location:

Preferred name:

NM_000271.5(NPC1):c.2683dup (p.Glu895fs)

HGVS:

NC_000018.10:g.23539924dup
NG_012795.1:g.51695dup
NM_000271.5:c.2683dupMANE SELECT
NP_000262.2:p.Glu895fs
NC_000018.9:g.21119886_21119887insC
NC_000018.9:g.21119888dup
NM_000271.4:c.2683dup
NM_000271.4:c.2683dupG

Protein change:

E895fs

Links:

dbSNP: rs1555633326

NCBI 1000 Genomes Browser:

rs1555633326

Molecular consequence:

NM_000271.5:c.2683dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Niemann-Pick disease, type C1
Synonyms:: NIEMANN-PICK DISEASE WITHOUT SPHINGOMYELINASE DEFICIENCY; Niemann-Pick disease with cholesterol esterification block; Niemann-Pick disease, chronic neuronopathic form; See all synonyms [MedGen]
Identifiers:: MONDO: MONDO:0009757; MedGen: C3179455; Orphanet: 646; OMIM: 257220

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000791368	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (May 9, 2017)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV003442629	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jul 8, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 26981555, 9211850, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000791368

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(May 9, 2017)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Citation Link,

SCV003442629

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jul 8, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

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
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Rapid Diagnosis of 83 Patients with Niemann Pick Type C Disease and Related Cholesterol Transport Disorders by Cholestantriol Screening.

Reunert J, Fobker M, Kannenberg F, Du Chesne I, Plate M, Wellhausen J, Rust S, Marquardt T.

EBioMedicine. 2016 Feb;4:170-5. doi: 10.1016/j.ebiom.2015.12.018.

PubMed [citation]

PMID:: 26981555
PMCID:: PMC4776073

Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.

Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ.

Science. 1997 Jul 11;277(5323):232-5.

PubMed [citation]

PMID:: 9211850

See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV000791368.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003442629.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 551834). This variant is also known as c.2683insG (fs917X). This premature translational stop signal has been observed in individual(s) with Niemann-Pick Type C (PMID: 26981555). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu895Glyfs*23) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850).

#	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: Sep 29, 2024

ClinVar

Relating variation to medicine