NM_000271.5(NPC1):c.1211G>A (p.Arg404Gln) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jul 26, 2024
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:: RCV000255152.6

Allele description [Variation Report for NM_000271.5(NPC1):c.1211G>A (p.Arg404Gln)]

NM_000271.5(NPC1):c.1211G>A (p.Arg404Gln)

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.1211G>A (p.Arg404Gln)

HGVS:

NC_000018.10:g.23556358C>T
NG_012795.1:g.35260G>A
NM_000271.5:c.1211G>AMANE SELECT
NP_000262.2:p.Arg404Gln
NC_000018.9:g.21136322C>T
NM_000271.4:c.1211G>A
O15118:p.Arg404Gln

Protein change:

R404Q

Links:

UniProtKB: O15118#VAR_043194; dbSNP: rs139751448

NCBI 1000 Genomes Browser:

rs139751448

Molecular consequence:

NM_000271.5:c.1211G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000321923	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Jul 26, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000321923

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Jul 26, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From GeneDx, SCV000321923.10

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

Description

Relatively common in affected patients, occurring on 3.1% of NPC1 alleles (PMID: 12955717); Published functional studies demonstrate R404Q significantly decreased binding to NPC2 compared the wild-type protein (PMID: 22065762); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 12974729, 27307437, 26666848, 11333381, 10480349, 15465421, 11545687, 30188717, 11349231, 27581084, 19744920, 26981555, 32222928, 32317543, 38178268, 12955717, 22065762)

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

Last Updated: Sep 29, 2024

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