NM_000277.2(PAH):c.1089delG (p.Lys363Asnfs) AND Phenylketonuria

This record was updated by the submitter. Please see the current version.

Germline classification:: Conflicting classifications of pathogenicity (2 submissions)
Last evaluated:: Oct 14, 2016
Review status:: criteria provided, conflicting classifications

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:: RCV000169397.1

Allele description

NM_000277.2(PAH):c.1089delG (p.Lys363Asnfs)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.2(PAH):c.1089delG (p.Lys363Asnfs)

HGVS:

NC_000012.12:g.102843756delC
NG_008690.2:g.119655delG
NM_000277.2:c.1089delG
NP_000268.1:p.Lys363Asnfs
NC_000012.11:g.103237534delC
NM_000277.1:c.1089delG

Links:

dbSNP: rs5030654

NCBI 1000 Genomes Browser:

rs5030654

Molecular consequence:

NM_000277.2:c.1089delG - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Phenylketonuria (PKU)
Synonyms:: Phenylketonurias; Classic phenylketonuria
Identifiers:: MedGen: C0031485; Orphanet: 716; OMIM: 261600

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000220793	Counsyl	criteria provided, single submitter (Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))	Likely pathogenic (Oct 14, 2014)	unknown	literature only	PubMed (8) [See all records that cite these PMIDs] 24048906, 17096675, 8659548, 21147011, 20920871, 22513348, 9781015, 19394257 Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015), Citation Link,
SCV000696425	Laboratory Corporation of America	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 14, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 21147011, 8659548 LabCorp Variant Classification Summary - May 2015.docx Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000220793

Counsyl

criteria provided, single submitter

(Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015))

Likely pathogenic
(Oct 14, 2014)

unknown

literature only

PubMed (8)
[See all records that cite these PMIDs]

Counsyl Autosomal and X-linked Recessive Disease Classification criteria (2015),

Citation Link,

SCV000696425

Laboratory Corporation of America

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 14, 2016)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

LabCorp Variant Classification Summary - May 2015.docx

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Mutation analysis of PAH gene in patients with PKU in western Iran and its association with polymorphisms: identification of four novel mutations.

Alibakhshi R, Moradi K, Mohebbi Z, Ghadiri K.

Metab Brain Dis. 2014 Mar;29(1):131-8. doi: 10.1007/s11011-013-9432-0. Epub 2013 Sep 19.

PubMed [citation]

PMID:: 24048906

Molecular epidemiology of phenylalanine hydroxylase deficiency in Southern Italy: a 96% detection rate with ten novel mutations.

Daniele A, Cardillo G, Pennino C, Carbone MT, Scognamiglio D, Correra A, Pignero A, Castaldo G, Salvatore F.

Ann Hum Genet. 2007 Mar;71(Pt 2):185-93. Epub 2006 Nov 10.

PubMed [citation]

PMID:: 17096675

See all PubMed Citations (8)

Details of each submission

From Counsyl, SCV000220793.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (8)

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

From Laboratory Corporation of America, SCV000696425.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: The PAH c.1089delG (p.Lys363Glnfs) variant results in a premature termination codon, predicted to cause a truncated or absent PAH protein due to nonsense mediated decay, which are commonly known mechanisms for disease. One in silico tool predicts a damaging outcome for this variant. This variant has been reported in numerous PKU and HPA patients and is absent in 121252 control chromosomes. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.

#	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: Apr 27, 2018

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