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NM_000277.3(PAH):c.981T>G (p.Phe327Leu) AND Phenylketonuria

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Apr 3, 2020
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV001199991.1

Allele description [Variation Report for NM_000277.3(PAH):c.981T>G (p.Phe327Leu)]

NM_000277.3(PAH):c.981T>G (p.Phe327Leu)

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.981T>G (p.Phe327Leu)
HGVS:
  • NC_000012.12:g.102844420A>C
  • NG_008690.2:g.118991T>G
  • NM_000277.1(PAH):c.981T>G
  • NM_000277.3:c.981T>GMANE SELECT
  • NM_001354304.2:c.981T>G
  • NP_000268.1:p.Phe327Leu
  • NP_001341233.1:p.Phe327Leu
  • NC_000012.11:g.103238198A>C
  • NM_000277.1(PAH):c.981T>G
  • NM_000277.1:c.981T>G
  • p.Phe327Leu
Protein change:
F327L
Links:
dbSNP: rs199475642
NCBI 1000 Genomes Browser:
rs199475642
Molecular consequence:
  • NM_000277.3:c.981T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.981T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Phenylketonuria (PKU)
Synonyms:
Phenylketonurias; Oligophrenia phenylpyruvica; Folling disease
Identifiers:
MONDO: MONDO:0009861; MedGen: C0031485; Orphanet: 716; OMIM: 261600

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001370827ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)
Uncertain significance
(Apr 3, 2020)
germlinecuration

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

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Phenylketonuria mutations in Germany.

Zschocke J, Hoffmann GF.

Hum Genet. 1999 May;104(5):390-8.

PubMed [citation]
PMID:
10394930

A European multicenter study of phenylalanine hydroxylase deficiency: classification of 105 mutations and a general system for genotype-based prediction of metabolic phenotype.

Guldberg P, Rey F, Zschocke J, Romano V, François B, Michiels L, Ullrich K, Hoffmann GF, Burgard P, Schmidt H, Meli C, Riva E, Dianzani I, Ponzone A, Rey J, Güttler F.

Am J Hum Genet. 1998 Jul;63(1):71-9. Erratum in: Am J Hum Genet 1998 Oct;63(4):1252-3.

PubMed [citation]
PMID:
9634518
PMCID:
PMC1377241

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001370827.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (2)

Description

The c.981T>G (p.Phe327Leu) variant in PAH has been reported in a German patient with classic PKU (BH4 deficiency excluded) (PMID: 9634518, 10394930) This variant is absent from population databases. Multiple lines of computational evidence support a deleterious effect. In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PP3.

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

Last Updated: Apr 23, 2022