NM_000439.5(PCSK1):c.541T>C (p.Tyr181His) AND Obesity due to prohormone convertase I deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 27, 2017
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:: RCV001156476.4

Allele description [Variation Report for NM_000439.5(PCSK1):c.541T>C (p.Tyr181His)]

NM_000439.5(PCSK1):c.541T>C (p.Tyr181His)

Genes:

CAST:calpastatin [Gene - OMIM - HGNC]
PCSK1:proprotein convertase subtilisin/kexin type 1 [Gene - OMIM - HGNC]
LOC101929710:uncharacterized LOC101929710 [Gene]

Variant type:

single nucleotide variant

Cytogenetic location:

5q15

Genomic location:

Preferred name:

NM_000439.5(PCSK1):c.541T>C (p.Tyr181His)

HGVS:

NC_000005.10:g.96423315A>G
NG_021161.1:g.14967T>C
NM_000439.5:c.541T>CMANE SELECT
NM_001177875.2:c.400T>C
NP_000430.3:p.Tyr181His
NP_001171346.1:p.Tyr134His
NC_000005.9:g.95759019A>G
NM_000439.4:c.541T>C

Protein change:

Y134H

Links:

dbSNP: rs145592525

NCBI 1000 Genomes Browser:

rs145592525

Molecular consequence:

NM_000439.5:c.541T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001177875.2:c.400T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Obesity due to prohormone convertase I deficiency
Synonyms:: OBESITY AND ENDOCRINOPATHY DUE TO IMPAIRED PROCESSING OF PROHORMONES; Proprotein convertase 1/3 deficiency
Identifiers:: MONDO: MONDO:0010961; MedGen: C1833053; Orphanet: 71528; OMIM: 600955

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001317975	Illumina Laboratory Services, Illumina	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Uncertain significance (Apr 27, 2017)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23383060, 22210313 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001317975

Illumina Laboratory Services, Illumina

criteria provided, single submitter

(ICSL Variant Classification Criteria 13 December 2019)

Uncertain significance
(Apr 27, 2017)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

Functional consequences of a novel variant of PCSK1.

Pickett LA, Yourshaw M, Albornoz V, Chen Z, Solorzano-Vargas RS, Nelson SF, Martín MG, Lindberg I.

PLoS One. 2013;8(1):e55065. doi: 10.1371/journal.pone.0055065. Epub 2013 Jan 28.

PubMed [citation]

PMID:: 23383060
PMCID:: PMC3557230

Heterozygous mutations causing partial prohormone convertase 1 deficiency contribute to human obesity.

Creemers JW, Choquet H, Stijnen P, Vatin V, Pigeyre M, Beckers S, Meulemans S, Than ME, Yengo L, Tauber M, Balkau B, Elliott P, Jarvelin MR, Van Hul W, Van Gaal L, Horber F, Pattou F, Froguel P, Meyre D.

Diabetes. 2012 Feb;61(2):383-90. doi: 10.2337/db11-0305. Epub 2011 Dec 30.

PubMed [citation]

PMID:: 22210313
PMCID:: PMC3266396

Details of each submission

From Illumina Laboratory Services, Illumina, SCV001317975.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

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

Last Updated: Oct 13, 2024

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