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NM_000271.5(NPC1):c.451_452del (p.Ser151fs) AND Niemann-Pick disease, type C

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 20, 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:
RCV001731880.1

Allele description [Variation Report for NM_000271.5(NPC1):c.451_452del (p.Ser151fs)]

NM_000271.5(NPC1):c.451_452del (p.Ser151fs)

Gene:
NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]
Variant type:
Microsatellite
Cytogenetic location:
18q11.2
Genomic location:
Preferred name:
NM_000271.5(NPC1):c.451_452del (p.Ser151fs)
HGVS:
  • NC_000018.10:g.23568834CT[1]
  • NC_000018.9:g.21148798_21148799del
  • NG_012795.1:g.22781AG[1]
  • NM_000271.5:c.451_452delMANE SELECT
  • NP_000262.2:p.Ser151fs
  • NC_000018.9:g.21148798CT[1]
  • NC_000018.9:g.21148798_21148799del
  • NC_000018.9:g.21148798_21148799delCT
  • NM_000271.4:c.451_452del
  • NM_000271.4:c.451_452delAG
Protein change:
S151fs
Links:
dbSNP: rs749012588
NCBI 1000 Genomes Browser:
rs749012588
Molecular consequence:
  • NM_000271.5:c.451_452del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV001983442Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Sep 20, 2021) 		germlineclinical testing

PubMed (8)
[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

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

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
See all PubMed Citations (8)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001983442.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (8)

Description

Variant summary: NPC1 c.451_452delAG (p.Ser151PhefsX18) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant allele was found at a frequency of 4e-06 in 251408 control chromosomes (gnomAD). c.451_452delAG has been reported in the literature in individuals affected with Niemann-Pick Disease Type C, including one homozygote (Sun_2001, Garver_2010, Mahmound_2019, Polese-Bonatto_2019). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=2) and likely pathogenic (n=1). 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: Oct 8, 2024