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NM_174936.4(PCSK9):c.2048dup (p.His683fs) AND Familial hypercholesterolemia

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Nov 20, 2023
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:
RCV003582168.1

Allele description [Variation Report for NM_174936.4(PCSK9):c.2048dup (p.His683fs)]

NM_174936.4(PCSK9):c.2048dup (p.His683fs)

Gene:
PCSK9:proprotein convertase subtilisin/kexin type 9 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
1p32.3
Genomic location:
Preferred name:
NM_174936.4(PCSK9):c.2048dup (p.His683fs)
HGVS:
  • NC_000001.11:g.55063553dup
  • NG_009061.1:g.29007dup
  • NM_001407240.1:c.2171dup
  • NM_001407241.1:c.2090dup
  • NM_001407242.1:c.2051dup
  • NM_001407243.1:c.1991dup
  • NM_001407244.1:c.1874dup
  • NM_001407245.1:c.1856dup
  • NM_001407246.1:c.1673dup
  • NM_001407247.1:c.1547dup
  • NM_174936.4:c.2048dupMANE SELECT
  • NP_001394169.1:p.His724fs
  • NP_001394170.1:p.His697fs
  • NP_001394171.1:p.His684fs
  • NP_001394172.1:p.His664fs
  • NP_001394173.1:p.His625fs
  • NP_001394174.1:p.His619fs
  • NP_001394175.1:p.His558fs
  • NP_001394176.1:p.His516fs
  • NP_777596.2:p.His683Glnfs
  • NP_777596.2:p.His683fs
  • LRG_275t1:c.2048dup
  • LRG_275:g.29007dup
  • LRG_275p1:p.His683Glnfs
  • NC_000001.10:g.55529226dup
  • NM_174936.3:c.2048dup
  • NR_110451.3:n.2329dup
  • NR_176318.1:n.2132dup
  • NR_176319.1:n.2607dup
  • NR_176320.1:n.2571dup
  • NR_176321.1:n.2286dup
  • NR_176322.1:n.2241dup
  • NR_176323.1:n.2160dup
  • NR_176324.1:n.2548dup
Protein change:
H516fs
Molecular consequence:
  • NM_001407240.1:c.2171dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407241.1:c.2090dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407242.1:c.2051dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407243.1:c.1991dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407244.1:c.1874dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407245.1:c.1856dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407246.1:c.1673dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001407247.1:c.1547dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_174936.4:c.2048dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NR_110451.3:n.2329dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176318.1:n.2132dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176319.1:n.2607dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176320.1:n.2571dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176321.1:n.2286dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176322.1:n.2241dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176323.1:n.2160dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_176324.1:n.2548dup - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Familial hypercholesterolemia
Identifiers:
MONDO: MONDO:0005439; MedGen: C0020445; OMIM: PS143890

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV004358834Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 20, 2023)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Rare and common variants of APOB and PCSK9 in Korean patients with extremely low low-density lipoprotein-cholesterol levels.

Lee CJ, Lee Y, Park S, Kang SM, Jang Y, Lee JH, Lee SH.

PLoS One. 2017;12(10):e0186446. doi: 10.1371/journal.pone.0186446.

PubMed [citation]
PMID:
29036232
PMCID:
PMC5643101

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 Color Diagnostics, LLC DBA Color Health, SCV004358834.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This variant inserts 1 nucleotide in exon 12 of the PCSK9 gene, creating a frameshift in the last exon and addition of 27 new amino acids before introducing a stop codon. This results in a protein product that is 17 amino acids longer than the normal protein product. This variant has been reported in one individual characterized as having extremely low circulating LDL-C levels (PMID: 29036232). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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

Last Updated: Sep 1, 2024