NM_000277.3(PAH):c.789C>G (p.Phe263Leu) AND not provided

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Dec 6, 2019
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:: RCV000089092.3

Allele description [Variation Report for NM_000277.3(PAH):c.789C>G (p.Phe263Leu)]

NM_000277.3(PAH):c.789C>G (p.Phe263Leu)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.789C>G (p.Phe263Leu)

Other names:

NM_000277.2(PAH):c.789C>G

HGVS:

NC_000012.12:g.102852868G>C
NG_008690.2:g.110543C>G
NM_000277.3:c.789C>GMANE SELECT
NM_001354304.2:c.789C>G
NP_000268.1:p.Phe263Leu
NP_001341233.1:p.Phe263Leu
NC_000012.11:g.103246646G>C
NC_000012.11:g.103246646G>C
NM_000277.1:c.789C>G
P00439:p.Phe263Leu

Protein change:

F263L

Links:

UniProtKB: P00439#VAR_000966; dbSNP: rs62642944

NCBI 1000 Genomes Browser:

rs62642944

Molecular consequence:

NM_000277.3:c.789C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.789C>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:: none provided; RECLASSIFIED - ADRA2C POLYMORPHISM; RECLASSIFIED - ADRB1 POLYMORPHISM
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119699	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV001780298	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 6, 2019)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119699

DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE

no classification provided

not provided

SCV001780298

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Pathogenic
(Dec 6, 2019)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only

Details of each submission

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119699.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	not provided	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV001780298.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Reported previously in association with phenylalanine hydroxylase deficiency (Takarada et al., 1993; Liu et al., 2015; Reblova et al., 2013); Published functional studies demonstrate a damaging effect with 5% residual PAH activity compared to wild-type (Lagler et al., 2010); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32668217, 26600521, 20705059, 7844888, 23357515, 8222245)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Feb 25, 2025

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