NM_000277.3(PAH):c.547_548delinsTT (p.Glu183Leu) AND Phenylketonuria

Germline classification:: Likely pathogenic (2 submissions)
Last evaluated:: Aug 11, 2019
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:: RCV000106359.3

Allele description [Variation Report for NM_000277.3(PAH):c.547_548delinsTT (p.Glu183Leu)]

NM_000277.3(PAH):c.547_548delinsTT (p.Glu183Leu)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Indel

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.547_548delinsTT (p.Glu183Leu)

HGVS:

NC_000012.12:g.102855294_102855295delinsAA
NG_008690.2:g.108116_108117delinsTT
NM_000277.3:c.547_548delinsTTMANE SELECT
NM_001354304.2:c.547_548delinsTT
NP_000268.1:p.Glu183Leu
NP_001341233.1:p.Glu183Leu
NC_000012.11:g.103249072_103249073delinsAA
NC_000012.12:g.102855294_102855295delTCinsAA
NM_000277.1:c.547_548delGAinsTT
NM_000277.2(PAH):c.547_548delGAinsTT
p.Glu183Leu

Protein change:

E183L

Links:

dbSNP: rs281865433

NCBI 1000 Genomes Browser:

rs281865433

Molecular consequence:

NM_000277.3:c.547_548delinsTT - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.547_548delinsTT - missense variant - [Sequence Ontology: SO:0001583]

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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Homo sapiens ASXL transcriptional regulator 2 (ASXL2), RefSeqGene (LRG_1421) on ...
Homo sapiens ASXL transcriptional regulator 2 (ASXL2), RefSeqGene (LRG_1421) on chromosome 2
gi|1159731471|ref|NG_052995.1||gnl| RG_1421

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000143859	Inserm U 954, Faculté de Médecine de Nancy	no assertion criteria provided	probable-pathogenic	unknown	not provided
SCV001146737	ClinGen PAH Variant Curation Expert Panel	reviewed by expert panel (ClinGen PAH ACMG Specifications v1)	Likely pathogenic (Aug 11, 2019)	germline	curation	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000143859

Inserm U 954, Faculté de Médecine de Nancy

no assertion criteria provided

probable-pathogenic

unknown

not provided

SCV001146737

ClinGen PAH Variant Curation Expert Panel

reviewed by expert panel

(ClinGen PAH ACMG Specifications v1)

Likely pathogenic
(Aug 11, 2019)

germline

curation

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	not provided	not provided	not provided	not provided	not provided	1	not provided	literature only
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	curation

Citations

PubMed

Genotype-phenotype associations in French patients with phenylketonuria and importance of genotype for full assessment of tetrahydrobiopterin responsiveness.

Jeannesson-Thivisol E, Feillet F, Chéry C, Perrin P, Battaglia-Hsu SF, Herbeth B, Cano A, Barth M, Fouilhoux A, Mention K, Labarthe F, Arnoux JB, Maillot F, Lenaerts C, Dumesnil C, Wagner K, Terral D, Broué P, de Parscau L, Gay C, Kuster A, Bédu A, et al.

Orphanet J Rare Dis. 2015 Dec 15;10:158. doi: 10.1186/s13023-015-0375-x.

PubMed [citation]

PMID:: 26666653
PMCID:: PMC5024853

Details of each submission

From Inserm U 954, Faculté de Médecine de Nancy, SCV000143859.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	not provided	not provided

Description

Converted during submission to Likely pathogenic.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	not provided	1	not provided	not provided		not provided	not provided	not provided	not provided

From ClinGen PAH Variant Curation Expert Panel, SCV001146737.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (1)

Description

The c.547_548delGAinsTT PAH variant has been identified in at least one patient with classic PKU (PMID: 26666653). It was detected in trans with the pathogenic variant c.143T>C; p.Leu48Ser (ClinVar 608). This variant is absent from 1000G, ESP, and gnomAD databases. It is predicted deleterious in multiple in silico models. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4, PM2, PM3, PP3.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 23, 2024

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