U.S. flag

An official website of the United States government

NM_000439.5(PCSK1):c.1961G>A (p.Arg654Gln) AND PCSK1-related disorder

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Mar 4, 2024
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV004747571.1

Allele description [Variation Report for NM_000439.5(PCSK1):c.1961G>A (p.Arg654Gln)]

NM_000439.5(PCSK1):c.1961G>A (p.Arg654Gln)

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.1961G>A (p.Arg654Gln)
HGVS:
  • NC_000005.10:g.96393302C>T
  • NG_021161.1:g.44980G>A
  • NM_000439.5:c.1961G>AMANE SELECT
  • NM_001177875.2:c.1820G>A
  • NM_001423250.1:c.-175+13650C>T
  • NM_001423251.1:c.-175+13650C>T
  • NM_001423252.1:c.-175+13650C>T
  • NM_001423253.1:c.-103+13650C>T
  • NM_001423254.1:c.-175+13650C>T
  • NM_001423255.1:c.-175+13650C>T
  • NM_001423256.1:c.-175+13650C>T
  • NM_001423257.1:c.-175+13650C>T
  • NM_001423258.1:c.-40+13650C>T
  • NM_001423259.1:c.-175+13650C>T
  • NM_001423260.1:c.-175+13650C>T
  • NP_000430.3:p.Arg654Gln
  • NP_001171346.1:p.Arg607Gln
  • NC_000005.9:g.95729006C>T
  • NM_000439.4:c.1961G>A
Protein change:
R607Q
Molecular consequence:
  • NM_001423250.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423251.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423252.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423253.1:c.-103+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423254.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423255.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423256.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423257.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423258.1:c.-40+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423259.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001423260.1:c.-175+13650C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000439.5:c.1961G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001177875.2:c.1820G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
PCSK1-related disorder
Synonyms:
PCSK1-related condition
Identifiers:

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005342251PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Uncertain significance
(Mar 4, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV005342251.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The PCSK1 c.1961G>A variant is predicted to result in the amino acid substitution p.Arg654Gln. This variant was observed in a cohort of obese individuals, and in vitro functional studies show inconclusive evidence of loss of function (Table 3 and Supplemental Data Set, Shah et al. 2023. PubMed ID: 36864747; Table 1, Folon et al. 2023. PubMed ID: 36822744). This variant is reported in 0.0054% of alleles in individuals of European (non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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

Last Updated: Oct 26, 2024