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NM_000271.5(NPC1):c.2524T>C (p.Phe842Leu) AND NPC1-related disorder

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Dec 20, 2023
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:
RCV003952965.1

Allele description [Variation Report for NM_000271.5(NPC1):c.2524T>C (p.Phe842Leu)]

NM_000271.5(NPC1):c.2524T>C (p.Phe842Leu)

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.2524T>C (p.Phe842Leu)
HGVS:
  • NC_000018.10:g.23540528A>G
  • NG_012795.1:g.51090T>C
  • NM_000271.5:c.2524T>CMANE SELECT
  • NP_000262.2:p.Phe842Leu
  • NC_000018.9:g.21120492A>G
  • NM_000271.4:c.2524T>C
Protein change:
F842L
Links:
dbSNP: rs190298665
NCBI 1000 Genomes Browser:
rs190298665
Molecular consequence:
  • NM_000271.5:c.2524T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
NPC1-related disorder
Synonyms:
NPC1-related condition
Identifiers:

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004767838PreventionGenetics, part of Exact Sciences
criteria provided, single submitter

(ACMG Guidelines, 2015)
Likely pathogenic
(Dec 20, 2023)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV004767838.1

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

Description

The NPC1 c.2524T>C variant is predicted to result in the amino acid substitution p.Phe842Leu. This variant has been reported in the compound heterozygous state in an individual with adult-onset Niemann-Pick disease type C (Zeiger et al. 2018. PubMed ID: 29453517) and was also identified in the analysis of a large sequencing dataset that did not include individuals with Niemann-Pick disease (Wassif et al. 2015. PubMed ID: 25764212). Additionally, this variant was seen in the compound heterozygous state in a patient at PreventionGenetics with biochemical findings that confirmed the diagnosis of Niemann-Pick disease. In summary, we interpret this variant as likely pathogenic.

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

Last Updated: May 19, 2024