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NM_000271.5(NPC1):c.2670C>G (p.Tyr890Ter) AND Niemann-Pick disease, type C

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Aug 3, 2017
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:
RCV000588008.1

Allele description [Variation Report for NM_000271.5(NPC1):c.2670C>G (p.Tyr890Ter)]

NM_000271.5(NPC1):c.2670C>G (p.Tyr890Ter)

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.2670C>G (p.Tyr890Ter)
HGVS:
  • NC_000018.10:g.23539936G>C
  • NG_012795.1:g.51682C>G
  • NM_000271.5:c.2670C>GMANE SELECT
  • NP_000262.2:p.Tyr890Ter
  • NC_000018.9:g.21119900G>C
  • NM_000271.4:c.2670C>G
Protein change:
Y890*
Links:
dbSNP: rs780592540
NCBI 1000 Genomes Browser:
rs780592540
Molecular consequence:
  • NM_000271.5:c.2670C>G - nonsense - [Sequence Ontology: SO:0001587]

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
SCV000696417Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Likely pathogenic
(Aug 3, 2017) 		germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx

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 C variant detection by altered sphingolipid trafficking and correlation with mutations within a specific domain of NPC1.

Sun X, Marks DL, Park WD, Wheatley CL, Puri V, O'Brien JF, Kraft DL, Lundquist PA, Patterson MC, Pagano RE, Snow K.

Am J Hum Genet. 2001 Jun;68(6):1361-72. Epub 2001 May 9.

PubMed [citation]
PMID:
11349231
PMCID:
PMC1226123

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696417.1

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

Description

Variant summary: The c.2670 (p.Tyr890*) variant in NPC1 gene is a nonsense change that results in the loss of the 389 amino acids of the protein (~30%). This change is predicted to cause loss of normal protein function through protein truncation or nonsense-mediated mRNA decay. The variant is present in the large control population dataset of ExAC at a low frequency of 8.238e-06 (1/121384 chrs tested), which does not exceed the maximal expected frequency of a pathogenic allele (0.0027) in this gene. The variant has been identified in compound heterozygosity with known pathogenic allele in affected siblings presented with the classical biochemical phenotype NPC-1 characterized by massive lysosomal/ LE accumulation of unesterified cholesterol in cultured fibroblasts. Taken together, the variant was classified as Likely Pathogenic.

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

Last Updated: Sep 29, 2024