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NM_000277.3(PAH):c.833C>A (p.Thr278Asn)

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Interpretation:
Pathogenic/Likely pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
3 (Most recent: Mar 6, 2020)
Last evaluated:
Oct 28, 2019
Accession:
VCV000102862.2
Variation ID:
102862
Description:
single nucleotide variant
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NM_000277.3(PAH):c.833C>A (p.Thr278Asn)

Allele ID
108598
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
12q23.2
Genomic location
12: 102852824 (GRCh38) GRCh38 UCSC
12: 103246602 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000012.11:g.103246602G>T
NC_000012.12:g.102852824G>T
NM_000277.3:c.833C>A MANE Select NP_000268.1:p.Thr278Asn missense
... more HGVS
Protein change
T278N
Other names
-
Canonical SPDI
NC_000012.12:102852823:G:T
Functional consequence
-
Global minor allele frequency (GMAF)
-

Allele frequency
-
Links
ClinGen: CA229802
UniProtKB: P00439#VAR_000979
dbSNP: rs62507262
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 2 criteria provided, multiple submitters, no conflicts Oct 28, 2019 RCV000665406.2
not provided 1 no assertion provided - RCV000089123.1
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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
1091 1120

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Oct 28, 2019)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: germline
Women's Health and Genetics/Laboratory Corporation of America, LabCorp
Accession: SCV001361333.1
Submitted: (Mar 06, 2020)
Evidence details
Publications
PubMed (5)
Comment:
Variant summary: PAH c.833C>A (p.Thr278Asn) results in a non-conservative amino acid change located in the Eukaryotic phenylalanine-4-hydroxylase, catalytic domain (IPR041912) of the encoded protein sequence. … (more)
Likely pathogenic
(Feb 03, 2017)
criteria provided, single submitter
Method: clinical testing
Phenylketonuria
Allele origin: unknown
Counsyl
Accession: SCV000789524.1
Submitted: (Jul 10, 2018)
Evidence details
Publications
PubMed (9)
not provided
(-)
no assertion provided
Method: not provided
not provided
Allele origin: not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE
Accession: SCV000119731.1
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
Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness. Jeannesson-Thivisol E Orphanet journal of rare diseases 2015 PMID: 26666653
Mutation spectrum of six genes in Chinese phenylketonuria patients obtained through next-generation sequencing. Gu Y PloS one 2014 PMID: 24705691
Accurate molecular diagnosis of phenylketonuria and tetrahydrobiopterin-deficient hyperphenylalaninemias using high-throughput targeted sequencing. Trujillano D European journal of human genetics : EJHG 2014 PMID: 23942198
Phenylalanine hydroxylase deficiency in the Slovak population: genotype-phenotype correlations and genotype-based predictions of BH4-responsiveness. Polak E Gene 2013 PMID: 23764561
Chaperone-like therapy with tetrahydrobiopterin in clinical trials for phenylketonuria: is genotype a predictor of response? Sarkissian CN JIMD reports 2012 PMID: 23430918
Incidence of BH4-responsiveness in phenylalanine-hydroxylase-deficient Italian patients. Fiori L Molecular genetics and metabolism 2005 PMID: 16198137
Structural studies on phenylalanine hydroxylase and implications toward understanding and treating phenylketonuria. Erlandsen H Pediatrics 2003 PMID: 14654665
PAH gene mutations in the Sicilian population: association with minihaplotypes and expression analysis. Mirisola MG Molecular genetics and metabolism 2001 PMID: 11708866
The structural basis of phenylketonuria. Erlandsen H Molecular genetics and metabolism 1999 PMID: 10527663
Mutational spectrum of phenylalanine hydroxylase deficiency in Sicily: implications for diagnosis of hyperphenylalaninemia in southern Europe. Guldberg P Human molecular genetics 1993 PMID: 8268925

Text-mined citations for rs62507262...

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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 Jun 14, 2021