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NM_000277.3(PAH):c.1115_1116dup (p.Ala373fs) AND Phenylketonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 15, 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:
RCV003495980.2

Allele description [Variation Report for NM_000277.3(PAH):c.1115_1116dup (p.Ala373fs)]

NM_000277.3(PAH):c.1115_1116dup (p.Ala373fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.1115_1116dup (p.Ala373fs)
HGVS:
  • NC_000012.12:g.102843730_102843731dup
  • NG_008690.2:g.119681_119682dup
  • NM_000277.3:c.1115_1116dupMANE SELECT
  • NM_001354304.2:c.1115_1116dup
  • NP_000268.1:p.Ala373fs
  • NP_001341233.1:p.Ala373fs
  • NC_000012.11:g.103237506_103237507insTG
  • NC_000012.11:g.103237508_103237509dup
Protein change:
A373fs
Molecular consequence:
  • NM_000277.3:c.1115_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.1115_1116dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004325825Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Sep 15, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Molecular basis of phenylketonuria and related hyperphenylalaninemias: mutations and polymorphisms in the human phenylalanine hydroxylase gene.

Eisensmith RC, Woo SL.

Hum Mutat. 1992;1(1):13-23. Review.

PubMed [citation]
PMID:
1301187

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
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004325825.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This variant has not been reported in the literature in individuals affected with PAH-related conditions. This sequence change creates a premature translational stop signal (p.Ala373Glnfs*28) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024