NM_000271.5(NPC1):c.423_424dup (p.Lys142fs) AND Niemann-Pick disease type C1

Clinical significance:Pathogenic (Last evaluated: Sep 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000984200.3

Allele description [Variation Report for NM_000271.5(NPC1):c.423_424dup (p.Lys142fs)]

NM_000271.5(NPC1):c.423_424dup (p.Lys142fs)

Gene:
NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
18q11.2
Genomic location:
Preferred name:
NM_000271.5(NPC1):c.423_424dup (p.Lys142fs)
HGVS:
  • NC_000018.10:g.23568862_23568863dup
  • NG_012795.1:g.22755_22756dup
  • NM_000271.5:c.423_424dupMANE SELECT
  • NP_000262.2:p.Lys142fs
  • NC_000018.9:g.21148825_21148826insTC
  • NC_000018.9:g.21148826_21148827dup
  • NM_000271.4:c.423_424dup
  • NM_000271.4:c.423_424dupGA
Protein change:
K142fs
Links:
dbSNP: rs773941375
NCBI 1000 Genomes Browser:
rs773941375
Molecular consequence:
  • NM_000271.5:c.423_424dup - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Niemann-Pick disease type C1 (NPC1)
Synonyms:
NIEMANN-PICK DISEASE WITHOUT SPHINGOMYELINASE DEFICIENCY; Niemann-Pick disease with cholesterol esterification block; Niemann-Pick disease, chronic neuronopathic form; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009757; MedGen: C3179455; Orphanet: 646; OMIM: 257220

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001132258Counsylno assertion criteria providedLikely pathogenic
(Jan 2, 2014)
unknownclinical testing

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

SCV001579550Invitaecriteria provided, single submitter
Pathogenic
(Sep 7, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

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

Murine model of Niemann-Pick C disease: mutation in a cholesterol homeostasis gene.

Loftus SK, Morris JA, Carstea ED, Gu JZ, Cummings C, Brown A, Ellison J, Ohno K, Rosenfeld MA, Tagle DA, Pentchev PG, Pavan WJ.

Science. 1997 Jul 11;277(5323):232-5.

PubMed [citation]
PMID:
9211850
See all PubMed Citations (3)

Details of each submission

From Counsyl, SCV001132258.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownunknownnot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV001579550.1

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

Description

This sequence change creates a premature translational stop signal (p.Lys142Argfs*80) in the NPC1 gene. It is expected to result in an absent or disrupted protein product. This variant is present in population databases (rs773941375, ExAC 0.001%). This variant has been observed in individual(s) with Niemann-Pick Disease Type C (PMID: 12955717). ClinVar contains an entry for this variant (Variation ID: 503633). Loss-of-function variants in NPC1 are known to be pathogenic (PMID: 9211850). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 26, 2021

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