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NM_000271.5(NPC1):c.3467A>G (p.Asn1156Ser) AND Niemann-Pick disease, type C

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jan 24, 2023
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:
RCV003114174.3

Allele description [Variation Report for NM_000271.5(NPC1):c.3467A>G (p.Asn1156Ser)]

NM_000271.5(NPC1):c.3467A>G (p.Asn1156Ser)

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.3467A>G (p.Asn1156Ser)
HGVS:
  • NC_000018.10:g.23535479T>C
  • NG_012795.1:g.56139A>G
  • NM_000271.5:c.3467A>GMANE SELECT
  • NP_000262.2:p.Asn1156Ser
  • NC_000018.9:g.21115443T>C
  • NM_000271.4:c.3467A>G
  • O15118:p.Asn1156Ser
Protein change:
N1156S; ASN1156SER
Links:
UniProtKB: O15118#VAR_008838; OMIM: 607623.0003; dbSNP: rs28942105
NCBI 1000 Genomes Browser:
rs28942105
Molecular consequence:
  • NM_000271.5:c.3467A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Niemann-Pick disease, type C (NPC)
Identifiers:
MONDO: MONDO:0018982; MedGen: C0220756

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003800706Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Jan 24, 2023) 		germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Niemann-Pick type C disease: mutations of NPC1 gene and evidence of abnormal expression of some mutant alleles in fibroblasts.

Tarugi P, Ballarini G, Bembi B, Battisti C, Palmeri S, Panzani F, Di Leo E, Martini C, Federico A, Calandra S.

J Lipid Res. 2002 Nov;43(11):1908-19.

PubMed [citation]
PMID:
12401890

The National Niemann-Pick Type C1 Disease Database: correlation of lipid profiles, mutations, and biochemical phenotypes.

Garver WS, Jelinek D, Meaney FJ, Flynn J, Pettit KM, Shepherd G, Heidenreich RA, Vockley CM, Castro G, Francis GA.

J Lipid Res. 2010 Feb;51(2):406-15. doi: 10.1194/jlr.P000331. Epub 2009 Sep 9.

PubMed [citation]
PMID:
19744920
PMCID:
PMC2803243
See all PubMed Citations (4)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV003800706.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

Variant summary: NPC1 c.3467A>G (p.Asn1156Ser) 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 2e-05 in 248932 control chromosomes. c.3467A>G has been reported in the literature as a biallelic homozygous or compound heterozygous genotype in multiple individuals affected with Niemann-Pick Disease Type C (example, PMID: 9211849, 19744920, 26981555, 12401890). These data indicate that the variant is very likely to be associated with disease. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024