NM_000271.5(NPC1):c.2974G>C (p.Gly992Arg) AND Niemann-Pick disease, type C

Clinical significance:Pathogenic (Last evaluated: Apr 26, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000590044.1

Allele description [Variation Report for NM_000271.5(NPC1):c.2974G>C (p.Gly992Arg)]

NM_000271.5(NPC1):c.2974G>C (p.Gly992Arg)

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.2974G>C (p.Gly992Arg)
HGVS:
  • NC_000018.10:g.23538609C>G
  • NG_012795.1:g.53009G>C
  • NM_000271.5:c.2974G>CMANE SELECT
  • NP_000262.2:p.Gly992Arg
  • NC_000018.9:g.21118573C>G
  • NM_000271.3:c.2974G>C
  • NM_000271.4:c.2974G>C
  • O15118:p.Gly992Arg
Protein change:
G992R; GLY992ARG
Links:
UniProtKB: O15118#VAR_015566; OMIM: 607623.0013; dbSNP: rs80358254
NCBI 1000 Genomes Browser:
rs80358254
Molecular consequence:
  • NM_000271.5:c.2974G>C - 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000696418Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Pathogenic
(Apr 26, 2017)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Summary from all submissions

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

Citations

PubMed

Niemann-pick disease type C: new aspects in a long published family - partial manifestations in heterozygotes.

Harzer K, Beck-Wödl S, Bauer P.

JIMD Rep. 2014;12:25-9. doi: 10.1007/8904_2013_240. Epub 2013 Jul 3.

PubMed [citation]
PMID:
23821321
PMCID:
PMC3897806

The adult form of Niemann-Pick disease type C.

Sévin M, Lesca G, Baumann N, Millat G, Lyon-Caen O, Vanier MT, Sedel F.

Brain. 2007 Jan;130(Pt 1):120-33. Epub 2006 Sep 26. Review.

PubMed [citation]
PMID:
17003072
See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000696418.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

Variant summary: The NPC1 c.2974G>C (p.Gly992Arg) variant involves the alteration of a conserved nucleotide. 2/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 4/121558 control chromosomes at a frequency of 0.0000329, which does not exceed the estimated maximal expected allele frequency of a pathogenic NPC1 variant (0.0027735). This variant has been reported in NPC patients (mostly adult-onset) both as homozygote and compound heterozygote. Another variant involving the same nucleotide G2974A, causing the same amino acid change G992R, has also been reported in multiple affected individuals. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic/likely pathogenic. Taken together, this variant is classified as pathogenic.

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

Last Updated: Dec 2, 2021

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