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NM_000277.3(PAH):c.806del (p.Ile269fs)

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Interpretation:
Pathogenic​

Review status:
reviewed by expert panel FDA Recognized Database
Submissions:
7 (Most recent: Dec 28, 2020)
Last evaluated:
Aug 10, 2018
Accession:
VCV000102844.5
Variation ID:
102844
Description:
1bp deletion
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NM_000277.3(PAH):c.806del (p.Ile269fs)

Allele ID
108580
Variant type
Deletion
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102852851 (GRCh38) GRCh38 UCSC
12: 103246629 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103246629del
NC_000012.12:g.102852851del
NM_000277.3:c.806del MANE Select NP_000268.1:p.Ile269fs frameshift
... more HGVS
Protein change
I269fs
Other names
NM_000277.2(PAH):c.806delT
Canonical SPDI
NC_000012.12:102852850:A:
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00003
Links
ClinGen: CA229778
dbSNP: rs62508687
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 5 reviewed by expert panel Aug 10, 2018 RCV000153633.10
Pathogenic 2 criteria provided, single submitter Jun 14, 2017 RCV000089103.2
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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
PAH - - GRCh38
GRCh37
1103 1132

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Aug 10, 2018)
reviewed by expert panel
Method: curation
Phenylketonuria
(Autosomal recessive inheritance)
Allele origin: germline
ClinGen PAH Variant Curation Expert Panel
FDA Recognized Database
Accession: SCV000852125.3
Submitted: (Feb 25, 2019)
Evidence details
Publications
PubMed (1)
Other databases
https://erepo.clinicalgenome.org…
Comment:
PAH-specific ACMG/AMP criteria applied: PVS1: Frameshift variant; PM2: Extremely low frequency. gnomAD MAF=0.00007.; PP4: Detected in a PKU patient. BH4 deficiency not assessed. (PMID:9012412). In … (more)
Pathogenic
(May 02, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Invitae
Accession: SCV000629216.1
Submitted: (Oct 05, 2017)
Evidence details
Comment:
This sequence change deletes 1 nucleotide from exon 7 of the PAH mRNA (c.806delT), causing a frameshift at codon 269. This creates a premature translational … (more)
Pathogenic
(Jun 14, 2017)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics
Accession: SCV000203181.7
Submitted: (Sep 19, 2018)
Evidence details
Publications
PubMed (1)
Other databases
http://www.egl-eurofins.com/emvc…
Pathogenic
(Jun 06, 2019)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361063.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: PAH c.806delT (p.Ile269ThrfsX72) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein … (more)
Likely pathogenic
(Mar 03, 2016)
no assertion criteria provided
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Counsyl
Accession: SCV000485936.2
Submitted: (Aug 05, 2019)
Evidence details
Publications
PubMed (4)
Pathogenic
(Sep 16, 2020)
no assertion criteria provided
Method: clinical testing
Phenylketonuria
Allele origin: germline
Natera, Inc.
Accession: SCV001453103.1
Submitted: (Dec 28, 2020)
Evidence details
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE
Accession: SCV000119710.1
Submitted: (Mar 30, 2012)
Evidence details

Functional evidence

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There is no functional evidence in ClinVar for this variation. If you have generated functional data for this variation, please consider submitting that data to ClinVar.

Citations for this variant

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Title Author Journal Year Link
The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness. Ho G JIMD reports 2014 PMID: 24368688
Chaperone-like therapy with tetrahydrobiopterin in clinical trials for phenylketonuria: is genotype a predictor of response? Sarkissian CN JIMD reports 2012 PMID: 23430918
Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles. Dobrowolski SF Molecular genetics and metabolism 2007 PMID: 17502162
Sequence variation at the phenylalanine hydroxylase gene in the British Isles. Tyfield LA American journal of human genetics 1997 PMID: 9012412
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=PAH - - - -
https://erepo.clinicalgenome.org/evrepo/ui/interpretation/f5d8dc3f-dba0-4dc9-98cd-4a22b6a11a83 - - - -

Text-mined citations for rs62508687...

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These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Aug 27, 2021