NM_000271.5(NPC1):c.2451_2454del (p.Leu817fs) AND Niemann-Pick disease, type C1

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Apr 4, 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:: RCV000664738.3

Allele description [Variation Report for NM_000271.5(NPC1):c.2451_2454del (p.Leu817fs)]

NM_000271.5(NPC1):c.2451_2454del (p.Leu817fs)

Gene:

NPC1:NPC intracellular cholesterol transporter 1 [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

18q11.2

Genomic location:

Preferred name:

NM_000271.5(NPC1):c.2451_2454del (p.Leu817fs)

HGVS:

NC_000018.10:g.23541129AACA[1]
NG_012795.1:g.50483GTTT[1]
NM_000271.4:c.2451_2454del
NM_000271.5:c.2451_2454delMANE SELECT
NP_000262.2:p.Leu817fs
NC_000018.9:g.21121093AACA[1]
NM_000271.4:c.2451_2454delGTTT

Protein change:

L817fs

Links:

dbSNP: rs1555633637

NCBI 1000 Genomes Browser:

rs1555633637

Molecular consequence:

NM_000271.5:c.2451_2454del - frameshift variant - [Sequence Ontology: SO:0001589]

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000788746	Counsyl	criteria provided, single submitter (Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))	Likely pathogenic (Jan 5, 2017)	unknown	clinical testing	Citation Link,
SCV004810346	Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Apr 4, 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

SCV000788746

Counsyl

criteria provided, single submitter

(Counsyl Autosomal Recessive and X-Linked Classification Criteria (2018))

Likely pathogenic
(Jan 5, 2017)

unknown

clinical testing

Citation Link,

SCV004810346

Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Apr 4, 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	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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 Counsyl, SCV000788746.1

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

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

From Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center, SCV004810346.1

#	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: Aug 4, 2024

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