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NM_000271.5(NPC1):c.352_353del (p.Gln119fs) AND Niemann-Pick disease, type C

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 4, 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:
RCV000781671.1

Allele description [Variation Report for NM_000271.5(NPC1):c.352_353del (p.Gln119fs)]

NM_000271.5(NPC1):c.352_353del (p.Gln119fs)

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.352_353del (p.Gln119fs)
HGVS:
  • NC_000018.10:g.23568933CT[1]
  • NG_012795.1:g.22682AG[1]
  • NM_000271.5:c.352_353delMANE SELECT
  • NP_000262.2:p.Gln119fs
  • NC_000018.9:g.21148897CT[1]
  • NC_000018.9:g.21148897_21148898del
  • NM_000271.4:c.352_353delAG
  • NM_000271.5:c.352_353delAGMANE SELECT
Protein change:
Q119fs
Links:
dbSNP: rs759075595
NCBI 1000 Genomes Browser:
rs759075595
Molecular consequence:
  • NM_000271.5:c.352_353del - 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
SCV000919894Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Pathogenic
(Dec 4, 2017) 		germlineclinical testing

PubMed (3)
[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 disease type C clinical database: cognitive and coordination deficits are early disease indicators.

Stampfer M, Theiss S, Amraoui Y, Jiang X, Keller S, Ory DS, Mengel E, Fischer C, Runz H.

Orphanet J Rare Dis. 2013 Feb 22;8:35. doi: 10.1186/1750-1172-8-35.

PubMed [citation]
PMID:
23433426
PMCID:
PMC3649939

NPC1 gene mutations in Japanese patients with Niemann-Pick disease type C.

Yamamoto T, Nanba E, Ninomiya H, Higaki K, Taniguchi M, Zhang H, Akaboshi S, Watanabe Y, Takeshima T, Inui K, Okada S, Tanaka A, Sakuragawa N, Millat G, Vanier MT, Morris JA, Pentchev PG, Ohno K.

Hum Genet. 1999 Jul-Aug;105(1-2):10-6.

PubMed [citation]
PMID:
10480349
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000919894.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: The NPC1 c.352_353delAG (p.Gln119ValfsX8) variant results in a premature termination codon, predicted to cause a truncated or absent NPC1 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 (e.g. c.1819C>T, p.Arg607X; c.3742_3745delCTCA, p.Leu1248fsX3). One in silico tool predicts a damaging outcome for this variant. This variant was found in 2/246198 control chromosomes at a frequency of 0.0000081, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). The variant has been reported in affected individuals in the literature, and one functional study showed the variant results in reduced mRNA due to non-sense mediated decay (Marcias-Vidal_2009). In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Sep 29, 2024