NM_000277.3(PAH):c.361T>C (p.Phe121Leu) AND Phenylketonuria

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Dec 14, 2021
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV003062537.3

Allele description [Variation Report for NM_000277.3(PAH):c.361T>C (p.Phe121Leu)]

NM_000277.3(PAH):c.361T>C (p.Phe121Leu)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.361T>C (p.Phe121Leu)

HGVS:

NC_000012.12:g.102877542A>G
NG_008690.2:g.85869T>C
NM_000277.3:c.361T>CMANE SELECT
NM_001354304.2:c.361T>C
NP_000268.1:p.Phe121Leu
NP_001341233.1:p.Phe121Leu
NC_000012.11:g.103271320A>G

Protein change:

F121L

Molecular consequence:

NM_000277.3:c.361T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.361T>C - 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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003441161	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 14, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 19915519, 23792259, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003441161

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 14, 2021)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutational spectrum of phenylketonuria in the Chinese Han population: a novel insight into the geographic distribution of the common mutations.

Zhu T, Qin S, Ye J, Qiu W, Han L, Zhang Y, Gu X.

Pediatr Res. 2010 Mar;67(3):280-5. doi: 10.1203/PDR.0b013e3181c9fb85.

PubMed [citation]

PMID:: 19915519

Mutation analysis in hyperphenylalaninemia patients from South Italy.

Trunzo R, Santacroce R, D'Andrea G, Longo V, De Girolamo G, Dimatteo C, Leccese A, Lillo V, Papadia F, Margaglione M.

Clin Biochem. 2013 Dec;46(18):1896-8. doi: 10.1016/j.clinbiochem.2013.06.009. Epub 2013 Jun 18.

PubMed [citation]

PMID:: 23792259

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003441161.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PAH protein function. This missense change has been observed in individual(s) with hyperphenylalaninemia (PMID: 19915519, 23792259). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces phenylalanine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 121 of the PAH protein (p.Phe121Leu).

#	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: Sep 29, 2024

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