NM_000271.5(NPC1):c.1430C>T (p.Thr477Met) AND Niemann-Pick disease, type C1

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jan 27, 2024
Review status:: criteria provided, conflicting classifications

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:: RCV001123522.12

Allele description

NM_000271.5(NPC1):c.1430C>T (p.Thr477Met)

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.1430C>T (p.Thr477Met)

HGVS:

NC_000018.10:g.23554881G>A
NG_012795.1:g.36737C>T
NM_000271.5:c.1430C>TMANE SELECT
NP_000262.2:p.Thr477Met
NC_000018.9:g.21134845G>A
NC_000018.9:g.21134845G>A
NM_000271.4:c.1430C>T

Protein change:

T477M

Links:

dbSNP: rs761459069

NCBI 1000 Genomes Browser:

rs761459069

Molecular consequence:

NM_000271.5:c.1430C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Niemann-Pick disease, type C1
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

Recent activity

Clear Turn Off Turn On

mechanosensitive ion channel domain-containing protein [Azospirillum sp. B510]
mechanosensitive ion channel domain-containing protein [Azospirillum sp. B510]
gi|502740398|ref|WP_012975382.1|

Protein
delta-sarcoglycan isoform X1 [Maylandia zebra]
delta-sarcoglycan isoform X1 [Maylandia zebra]
gi|1381367147|ref|XP_024659860.1|

Protein
Eliurus myoxinus voucher MR 156 cytochrome b (cytb) gene, partial cds; mitochond...
Eliurus myoxinus voucher MR 156 cytochrome b (cytb) gene, partial cds; mitochondrial
gi|515474862|gb|KF058129.1|

Nucleotide
LOC103568045 [Equus przewalskii]
LOC103568045 [Equus przewalskii]
Gene ID:103568045

Gene
SYK [Mustela nigripes]
SYK [Mustela nigripes]
Gene ID:132024902

Gene

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001282366	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link,
SCV002360049	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely benign (Jan 27, 2024)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001282366

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

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

Citation Link,

SCV002360049

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely benign
(Jan 27, 2024)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Niemann-Pick C disease gene mutations and age-related neurodegenerative disorders.

Zech M, Nübling G, Castrop F, Jochim A, Schulte EC, Mollenhauer B, Lichtner P, Peters A, Gieger C, Marquardt T, Vanier MT, Latour P, Klünemann H, Trenkwalder C, Diehl-Schmid J, Perneczky R, Meitinger T, Oexle K, Haslinger B, Lorenzl S, Winkelmann J.

PLoS One. 2013;8(12):e82879. doi: 10.1371/journal.pone.0082879.

PubMed [citation]

PMID:: 24386122
PMCID:: PMC3875432

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001282366.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Invitae, SCV002360049.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 28, 2024

ClinVar

Relating variation to medicine