NM_000271.5(NPC1):c.1843C>T (p.Arg615Cys) AND Inborn genetic diseases

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 18, 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:: RCV001265829.4

Allele description [Variation Report for NM_000271.5(NPC1):c.1843C>T (p.Arg615Cys)]

NM_000271.5(NPC1):c.1843C>T (p.Arg615Cys)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

18q11.2

Genomic location:

Preferred name:

NM_000271.5(NPC1):c.1843C>T (p.Arg615Cys)

HGVS:

NC_000018.10:g.23545064G>A
NG_012795.1:g.46554C>T
NM_000271.5:c.1843C>TMANE SELECT
NP_000262.2:p.Arg615Cys
NC_000018.9:g.21125028G>A
NM_000271.4:c.1843C>T

Protein change:

R615C

Links:

dbSNP: rs745777805

NCBI 1000 Genomes Browser:

rs745777805

Molecular consequence:

NM_000271.5:c.1843C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001444001	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Pathogenic (May 18, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 12955717, 26666848, 27928380, 30285904, 32222928 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001444001

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Pathogenic
(May 18, 2021)

germline

clinical testing

PubMed (5)
[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

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, O'Brien JF, Lundquist PA, Kraft DL, Vockley CW, Karnes PS, Patterson MC, Snow K.

Hum Mutat. 2003 Oct;22(4):313-25.

PubMed [citation]

PMID:: 12955717

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, Heptinstall L, Knight S, Strong K.

BMC Neurol. 2015 Dec 15;15:257. doi: 10.1186/s12883-015-0511-1.

PubMed [citation]

PMID:: 26666848
PMCID:: PMC4678528

See all PubMed Citations (5)

Details of each submission

From Ambry Genetics, SCV001444001.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

The c.1843C>T (p.R615C) alteration is located in coding exon 12 of the NPC1 gene. This alteration results from a C to T substitution at nucleotide position 1843, causing the arginine (R) at amino acid position 615 to be replaced by a cysteine (C). Based on data from the Genome Aggregation Database (gnomAD) database, the NPC1 c.1843C>T alteration was observed in 0.005% (13/251,472) of total alleles studied, with a frequency of 0.011% (2/18,394) in the East Asian subpopulation. This alteration has been reported in multiple unrelated patients with Niemann-Pick type C, confirmed by abnormal filipin staining and/or abnormal cholesterol esterification (Park, 2003; Imrie, 2015; Nadjar, 2018; Havla, 2020). This amino acid position is highly conserved in available vertebrate species. The p.R615C alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is 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: Sep 29, 2024

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