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NM_001395413.1(POR):c.1208G>A (p.Arg403His) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 26, 2021
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV001546288.15

Allele description [Variation Report for NM_001395413.1(POR):c.1208G>A (p.Arg403His)]

NM_001395413.1(POR):c.1208G>A (p.Arg403His)

Gene:
POR:cytochrome p450 oxidoreductase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7q11.23
Genomic location:
Preferred name:
NM_001395413.1(POR):c.1208G>A (p.Arg403His)
HGVS:
  • NC_000007.14:g.75984927G>A
  • NG_008930.1:g.74826G>A
  • NM_001367562.3:c.1208G>A
  • NM_001382655.3:c.1262G>A
  • NM_001382657.2:c.1208G>A
  • NM_001382658.3:c.1208G>A
  • NM_001382659.3:c.1208G>A
  • NM_001382662.3:c.1208G>A
  • NM_001395413.1:c.1208G>AMANE SELECT
  • NP_001354491.2:p.Arg403His
  • NP_001369584.2:p.Arg421His
  • NP_001369586.2:p.Arg403His
  • NP_001369587.2:p.Arg403His
  • NP_001369588.2:p.Arg403His
  • NP_001369591.2:p.Arg403His
  • NP_001382342.1:p.Arg403His
  • NC_000007.13:g.75614245G>A
  • NM_000941.2:c.1217G>A
Protein change:
R403H
Links:
dbSNP: rs72557929
NCBI 1000 Genomes Browser:
rs72557929
Molecular consequence:
  • NM_001367562.3:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382655.3:c.1262G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382657.2:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382658.3:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382659.3:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001382662.3:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001395413.1:c.1208G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001473361ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
criteria provided, single submitter

(ARUP Molecular Germline Variant Investigation Process)		Uncertain significance
(Mar 13, 2020) 		germlineclinical testing

Citation Link,

SCV001765784GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Jan 26, 2021) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

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

Details of each submission

From ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories, SCV001473361.1

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

Description

The POR c.1217G>A; p.Arg406His variant (rs72557929) is reported in the literature in a cohort of healthy individuals (Huang 2008). This variant is found in the non-Finnish European population with an overall allele frequency of 0.02% (23/124870 alleles) in the Genome Aggregation Database. The arginine at codon 406 is highly conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Functional analyses suggest the p.Arg406His variant protein supports normal activity of partner proteins but exhibits slightly reduced POR enzymatic activity (Agrawal 2008, Huang 2008), though it is unknown if this slight reduction is clinically significant. Due to limited information, the clinical significance of the p.Arg406His variant is uncertain at this time. References: Agrawal et al. Pharmacogenetics of P450 oxidoreductase: effect of sequence variants on activities of CYP1A2 and CYP2C19. Pharmacogenet Genomics. 2008 Jul;18(7):569-76. Huang et al. Genetics of P450 oxidoreductase: sequence variation in 842 individuals of four ethnicities and activities of 15 missense mutations. Proc Natl Acad Sci U S A. 2008 Feb 5;105(5):1733-8.

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

From GeneDx, SCV001765784.1

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

Description

In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not reported as pathogenic or benign in association with a disease to our our knowledge. However, identified in a healthy population and functional studies demonstrate a moderate reduction in protein activities in multiple enzymatic assays (Huang et al., 2008; Agrawal et al., 2008); This variant is associated with the following publications: (PMID: 27068427, 25133307, 18433346, 24847272, 23353702, 18930113, 18551037, 18230729)

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

Last Updated: Oct 8, 2024