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NM_000277.3(PAH):c.241_256del (p.Thr81fs) AND Phenylketonuria

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Oct 22, 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:
RCV001269056.2

Allele description [Variation Report for NM_000277.3(PAH):c.241_256del (p.Thr81fs)]

NM_000277.3(PAH):c.241_256del (p.Thr81fs)

Gene:
PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
12q23.2
Genomic location:
Preferred name:
NM_000277.3(PAH):c.241_256del (p.Thr81fs)
HGVS:
  • NC_000012.12:g.102894832_102894847del
  • NG_008690.2:g.68565_68580del
  • NM_000277.3:c.241_256delMANE SELECT
  • NM_001354304.2:c.241_256del
  • NP_000268.1:p.Thr81fs
  • NP_001341233.1:p.Thr81fs
  • NC_000012.11:g.103288610_103288625del
  • NM_000277.1:c.241_256del16
Protein change:
T81fs
Links:
dbSNP: rs63749677
NCBI 1000 Genomes Browser:
rs63749677
Molecular consequence:
  • NM_000277.3:c.241_256del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001354304.2:c.241_256del - 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
SCV001448251ClinGen PAH Variant Curation Expert Panel
reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)		Pathogenic
(Oct 22, 2020) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population.

Liang Y, Huang MZ, Cheng CY, Chao HK, Fwu VT, Chiang SH, Hsiao KJ, Niu DM, Su TS.

J Hum Genet. 2014 Mar;59(3):145-52. doi: 10.1038/jhg.2013.136. Epub 2014 Jan 9.

PubMed [citation]
PMID:
24401910

Mutation spectrum in Taiwanese patients with phenylalanine hydroxylase deficiency and a founder effect for the R241C mutation.

Chien YH, Chiang SC, Huang A, Chou SP, Tseng SS, Huang YT, Hwu WL.

Hum Mutat. 2004 Feb;23(2):206. doi: 10.1002/humu.9215.

PubMed [citation]
PMID:
14722928

Details of each submission

From ClinGen PAH Variant Curation Expert Panel, SCV001448251.1

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

Description

This c.241_256del (p.Thr81fs) variant in PAH has been reported in two patients with PKU, observed with two pathogenic variants: p.R241C, phase unknown (PMID: 14722928) and with p.V399V, phase unknown (PMID: 24401910). This variant is absent from controls is population databases. This is a frameshift variant in exon 3 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, PP4_moderate, and PM3.

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

Last Updated: Jun 23, 2024