NM_000271.5(NPC1):c.180G>T (p.Gln60His) AND not provided

Germline classification:: Conflicting classifications of pathogenicity (6 submissions)
Last evaluated:: Jul 1, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV000728354.26

Allele description [Variation Report for NM_000271.5(NPC1):c.180G>T (p.Gln60His)]

NM_000271.5(NPC1):c.180G>T (p.Gln60His)

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.180G>T (p.Gln60His)

Other names:

p.Gln60His

HGVS:

NC_000018.10:g.23573452C>A
NG_012795.1:g.18166G>T
NM_000271.5:c.180G>TMANE SELECT
NP_000262.2:p.Gln60His
NC_000018.9:g.21153416C>A
NM_000271.4:c.180G>T

Protein change:

Q60H

Links:

dbSNP: rs145666943

NCBI 1000 Genomes Browser:

rs145666943

Molecular consequence:

NM_000271.5:c.180G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000855913	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Jul 25, 2017)	germline	clinical testing	Citation Link,
SCV001809110	Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV001819373	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Jan 27, 2021)	germline	clinical testing	Citation Link,
SCV001958998	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Uncertain significance	germline	clinical testing
SCV004140868	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Likely benign (Jul 1, 2022)	germline	clinical testing	Citation Link,
SCV004224469	Mayo Clinic Laboratories, Mayo Clinic	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (May 3, 2022)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 24386122, 30556376, 31635081, 25741868

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	3	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

Zech M, Nübling G, Castrop F, Jochim A, Schulte EC, Mollenhauer B, Lichtner P, Peters A, Gieger C, Marquardt T, Vanier MT, Latour P, Klünemann H, Trenkwalder C, Diehl-Schmid J, Perneczky R, Meitinger T, Oexle K, Haslinger B, Lorenzl S, Winkelmann J.

PLoS One. 2013;8(12):e82879. doi: 10.1371/journal.pone.0082879.

PubMed [citation]

PMID:: 24386122
PMCID:: PMC3875432

Enrichment of pathogenic variants in genes associated with inborn errors of metabolism in psychiatric populations.

Sriretnakumar V, Harripaul R, Vincent JB, Kennedy JL, So J.

Am J Med Genet B Neuropsychiatr Genet. 2019 Jan;180(1):46-54. doi: 10.1002/ajmg.b.32702. Epub 2018 Dec 16.

PubMed [citation]

PMID:: 30556376

See all PubMed Citations (4)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000855913.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	not provided

#	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		2	not provided	not provided	not provided

From Genome Diagnostics Laboratory, Amsterdam University Medical Center - VKGL Data-share Consensus, SCV001809110.1

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

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

From GeneDx, SCV001819373.1

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

Description

This variant is associated with the following publications: (PMID: 31635081, 24386122, 30556376)

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

From Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001958998.1

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

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

From CeGaT Center for Human Genetics Tuebingen, SCV004140868.13

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

Description

NPC1: BP5

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

From Mayo Clinic Laboratories, Mayo Clinic, SCV004224469.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	clinical testing	PubMed (4)

Description

PP4, PM2, PM3

#	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		1	not provided	not provided	not provided

Last Updated: Apr 28, 2025

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