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NM_000277.3(PAH):c.690_691insG (p.Ser231fs) AND Phenylketonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 15, 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:
RCV001269079.2

Allele description [Variation Report for NM_000277.3(PAH):c.690_691insG (p.Ser231fs)]

NM_000277.3(PAH):c.690_691insG (p.Ser231fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Insertion
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.690_691insG (p.Ser231fs)
HGVS:
  • NC_000012.12:g.102855151_102855152insC
  • NG_008690.2:g.108259_108260insG
  • NM_000277.3:c.690_691insGMANE SELECT
  • NM_001354304.2:c.690_691insG
  • NP_000268.1:p.Ser231fs
  • NP_001341233.1:p.Ser231fs
  • NC_000012.11:g.103248929_103248930insC
Protein change:
S231fs
Links:
dbSNP: rs1875354018
NCBI 1000 Genomes Browser:
rs1875354018
Molecular consequence:
  • NM_000277.3:c.690_691insG - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.690_691insG - 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
SCV001448305ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Pathogenic
(Oct 15, 2020) 		germlinecuration

PubMed (1)
[See all records that cite this PMID]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China.

Liu N, Huang Q, Li Q, Zhao D, Li X, Cui L, Bai Y, Feng Y, Kong X.

BMC Med Genet. 2017 Oct 5;18(1):108. doi: 10.1186/s12881-017-0467-7. Erratum in: BMC Med Genet. 2018 Jan 9;19(1):6. doi: 10.1186/s12881-017-0516-2.

PubMed [citation]
PMID:
28982351
PMCID:
PMC5629770

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001448305.1

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

Description

This c.690_691insG (p.Ser231ValfsTer?) variant in PAH was reported in one patient with Hyperphenylalaninemia (PMID: 28982351). This variant is absent from controls in population databases. This is a frameshift variant in exon 6 out of 13 coding exons. The variant is predicted to undergo nonsense mediated mRNA decay (NMD), as it is not located in the 3’-most exon or the 3’-most 50 bp of the penultimate exon. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, and PP4.

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

Last Updated: Jun 23, 2024