NM_000941.3(POR):c.683C>T (p.Pro228Leu) AND none provided

Clinical significance:Uncertain significance (Last evaluated: Feb 12, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001282487.2

Allele description [Variation Report for NM_000941.3(POR):c.683C>T (p.Pro228Leu)]

NM_000941.3(POR):c.683C>T (p.Pro228Leu)

Gene:
POR:cytochrome p450 oxidoreductase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q11.23
Genomic location:
Preferred name:
NM_000941.3(POR):c.683C>T (p.Pro228Leu)
HGVS:
  • NC_000007.14:g.75981558C>T
  • NG_008930.1:g.71457C>T
  • NM_000941.3:c.683C>TMANE SELECT
  • NM_001382657.1:c.683C>T
  • NP_000932.3:p.Pro228Leu
  • NP_001354491.1:p.Pro228Leu
  • NP_001369584.1:p.Pro246Leu
  • NP_001369586.1:p.Pro228Leu
  • NP_001369587.1:p.Pro228Leu
  • NP_001369588.1:p.Pro228Leu
  • NP_001369591.1:p.Pro228Leu
  • NC_000007.13:g.75610876C>T
  • NC_000007.13:g.75610876C>T
  • NM_000941.2:c.683C>T
  • NM_001367562.1:c.683C>T
  • NM_001382655.1:c.737C>T
  • NM_001382658.1:c.683C>T
  • NM_001382659.1:c.683C>T
  • NM_001382662.1:c.683C>T
Protein change:
P228L
Links:
dbSNP: rs17853284
NCBI 1000 Genomes Browser:
rs17853284
Molecular consequence:
  • NM_000941.3:c.683C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382657.1:c.683C>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
none provided
Identifiers:
MedGen: CN235283

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000604908ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratoriescriteria provided, single submitter
Uncertain significance
(Feb 12, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV000604908.4

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

Description

The POR c.683C>T; p.Pro228Leu variant (rs17853284), which is part of the POR*36 allele (Gomes 2009), has been reported to have 40 to 100 percent P450 oxidoreductase activity in assays on CYP2C19, CYP17A1, NADPH Ox, Cyt c Red, CYP17A1, CYP3A4 and HO-1 enzymes (Agrawl 2008, Huang 2005, Marohnic 2001, Moutinho 2012, Pandey 2010), and 20 percent activity on CYP1A2 (Agrawal 2008). The p.Pro228Leu variant is listed in ClinVar (Variation ID: 436385), and is found in the general population with an overall allele frequency of 0.25% (689/277308 alleles, including a single homozygote) in the Genome Aggregation Database. The proline at position 228 is highly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Although the functional assays suggest that the p.Pro228Leu may be a benign polymorphism, there is insufficient information to determine its clinical significance with certainty. References: Agrawal V et al. Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19. Pharmacogenet Genomics. 2008; 18(7):569-76. Gomes A et al. Pharmacogenomics of human liver cytochrome P450 oxidoreductase: multifactorial analysis and impact on microsomal drug oxidation. Pharmacogenomics. 2009; 10(4):579-99. Huang N et al. Diversity and function of mutations in p450 oxidoreductase in patients with Antley-Bixler syndrome and disordered steroidogenesis. Am J Hum Genet. 2005; 76(5):729-49. Marohnic C et al. Mutations of human cytochrome P450 reductase differentially modulate heme oxygenase-1 activity and oligomerization. Arch Biochem Biophys. 2011;513(1):42-50. Moutinho D et al. Altered human CYP3A4 activity caused by Antley-Bixler syndrome-related variants of NADPH-cytochrome P450 oxidoreductase measured in a robust in vitro system. Drug Metab Dispos. 2012; 40(4):754-60. Pandey A et al. Altered heme catabolism by heme oxygenase-1 caused by mutations in human NADPH cytochrome P450 reductase. Biochem Biophys Res Commun. 2010; 400(3):374-8.

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

Last Updated: Dec 4, 2021

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