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NM_000277.3(PAH):c.941C>A (p.Pro314His)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
6 (Most recent: Jan 7, 2021)
Last evaluated:
Nov 5, 2019
Accession:
VCV000102907.5
Variation ID:
102907
Description:
single nucleotide variant
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NM_000277.3(PAH):c.941C>A (p.Pro314His)

Allele ID
108643
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102846923 (GRCh38) GRCh38 UCSC
12: 103240701 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
P00439:p.Pro314His
NC_000012.11:g.103240701G>T
NC_000012.12:g.102846923G>T
... more HGVS
Protein change
P314H
Other names
-
Canonical SPDI
NC_000012.12:102846922:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
Trans-Omics for Precision Medicine (TOPMed) 0.00001
Links
ClinGen: CA229867
UniProtKB: P00439#VAR_000997
dbSNP: rs62642940
Varsome
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic/Likely pathogenic 5 criteria provided, multiple submitters, no conflicts Nov 5, 2019 RCV000409567.6
not provided 1 no assertion provided - RCV000089171.1
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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
Likely pathogenic
(Jul 12, 2016)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Counsyl
Accession: SCV000486619.1
Submitted: (Nov 23, 2016)
Evidence details
Publications
PubMed (5)
Pathogenic
(Oct 08, 2014)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Genome Diagnostics Laboratory, University Medical Center Utrecht
Study: VKGL Data-share Consensus
Accession: SCV000744093.1
Submitted: (Apr 17, 2018)
Evidence details
Likely pathogenic
(Jan 04, 2016)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center
Study: VKGL Data-share Consensus
Accession: SCV000745571.1
Submitted: (Apr 09, 2018)
Evidence details
Pathogenic
(Aug 29, 2019)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001363421.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (4)
Comment:
Variant summary: PAH c.941C>A (p.Pro314His) results in a non-conservative amino acid change located in the catalytic domain (IPR041912) of the encoded protein sequence. Five of … (more)
Pathogenic
(Nov 05, 2019)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Invitae
Accession: SCV001414760.2
Submitted: (Jan 07, 2021)
Evidence details
Publications
PubMed (5)
Comment:
This sequence change replaces proline with histidine at codon 314 of the PAH protein (p.Pro314His). The proline residue is highly conserved and there is a … (more)
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE
Accession: SCV000119786.1
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
Mutational spectrum of the phenylalanine hydroxylase gene in patients with phenylketonuria in the central region of China. Zhang Z Scandinavian journal of clinical and laboratory investigation 2018 PMID: 29390883
Spectrum of PAH gene variants among a population of Han Chinese patients with phenylketonuria from northern China. Liu N BMC medical genetics 2017 PMID: 28982351
Phenylalanine hydroxylase deficiency in Mexico: genotype-phenotype correlations, BH4 responsiveness and evidence of a founder effect. Vela-Amieva M Clinical genetics 2015 PMID: 24941924
The mutation spectrum of the phenylalanine hydroxylase (PAH) gene and associated haplotypes reveal ethnic heterogeneity in the Taiwanese population. Liang Y Journal of human genetics 2014 PMID: 24401910
Tetrahydrobiopterin responsiveness in phenylketonuria: prediction with the 48-hour loading test and genotype. Anjema K Orphanet journal of rare diseases 2013 PMID: 23842451
Simultaneous assessment of the effects of exonic mutations on RNA splicing and protein functions. Ho PY Biochemical and biophysical research communications 2008 PMID: 18590700
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 American journal of human genetics 1998 PMID: 9634518
Phenylketonuria in The Netherlands: 93% of the mutations are detected by single-strand conformation analysis. van der Sijs-Bos CJ Human heredity 1996 PMID: 8807319

Text-mined citations for rs62642940...

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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 Sep 07, 2021