NM_000277.3(PAH):c.281TCA[1] (p.Ile95del) AND not provided

Germline classification:: Pathogenic (5 submissions)
Last evaluated:: Dec 16, 2020
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000078518.21

Allele description [Variation Report for NM_000277.3(PAH):c.281TCA[1] (p.Ile95del)]

NM_000277.3(PAH):c.281TCA[1] (p.Ile95del)

Gene:

PAH:phenylalanine hydroxylase [Gene - OMIM - HGNC]

Variant type:

Microsatellite

Cytogenetic location:

12q23.2

Genomic location:

Preferred name:

NM_000277.3(PAH):c.281TCA[1] (p.Ile95del)

HGVS:

NC_000012.12:g.102894801_102894803delTGA
NC_000012.12:g.102894803ATG[1]
NG_008690.2:g.68605TCA[1]
NM_000277.3:c.281TCA[1]MANE SELECT
NM_000277.3:c.284_286del
NM_001354304.2:c.281TCA[1]
NP_000268.1:p.Ile95del
NP_001341233.1:p.Ile95del
NC_000012.11:g.103288579_103288581del
NC_000012.11:g.103288581ATG[1]
NC_000012.12:g.102894801_102894803delTGA
NC_000012.12:g.102894803_102894805ATG[1]
NM_000277.1:c.283_285delATC
NM_000277.1:c.284_286delTCA
NM_000277.3(PAH):c.281_283TCA[1]MANE SELECT
NM_000277.3:c.284_286delMANE SELECT
NM_000277.3:c.284_286delTCAMANE SELECT
p.I95del

Protein change:

I95del

Links:

OMIM: 612349.0030; dbSNP: rs62508727

NCBI 1000 Genomes Browser:

rs62508727

Molecular consequence:

NM_000277.3:c.281TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001354304.2:c.281TCA[1] - inframe_deletion - [Sequence Ontology: SO:0001822]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000110374	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Feb 6, 2013)	germline	clinical testing	Citation Link,
SCV000119489	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV000239098	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Dec 16, 2020)	germline	clinical testing	Citation Link,
SCV000601712	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Pathogenic (Apr 7, 2017)	germline	clinical testing	PubMed (17) [See all records that cite these PMIDs] 1709636, 17935162, 25894915, 24705691, 24368688, 23430918, 20217238, 20457534, 19292873, 18985011, 17096675, 16256386, 14722928, 26666653, 26503515, 25255367, 26467025

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	not provided	not provided	not provided	not provided	not provided	2	not provided	literature only

Citations

PubMed

A 3-base pair in-frame deletion of the phenylalanine hydroxylase gene results in a kinetic variant of phenylketonuria.

Caillaud C, Lyonnet S, Rey F, Melle D, Frebourg T, Berthelon M, Vilarinho L, Vaz Osorio R, Rey J, Munnich A.

J Biol Chem. 1991 May 25;266(15):9351-4.

PubMed [citation]

PMID:: 1709636

Molecular genetics of tetrahydrobiopterin-responsive phenylalanine hydroxylase deficiency.

Zurflüh MR, Zschocke J, Lindner M, Feillet F, Chery C, Burlina A, Stevens RC, Thöny B, Blau N.

Hum Mutat. 2008 Jan;29(1):167-75.

PubMed [citation]

PMID:: 17935162

See all PubMed Citations (17)

Details of each submission

From Eurofins Ntd Llc (ga), SCV000110374.8

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

#	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		2	not provided	not provided	not provided

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119488.1

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

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

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119489.1

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

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

From GeneDx, SCV000239098.11

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

Description

In-frame deletion of 1 amino acid in a non-repeat region predicted to critically alter the protein; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports a deleterious effect on protein structure/function; Responsiveness to BH4 therapy is inconsistent (Zurfluh et al., 2008; Jeannesson-Thivisol et al., 2015); This variant is associated with the following publications: (PMID: 25894915, 19292873, 25255367, 14722928, 1709636, 17935162, 26503515, 24705691, 26666653, 19194782, 18985011, 17096675, 16256386, 24368688, 23430918, 20217238, 30487145, 31028937, 30747360, 32668217, 31589614, 32853555)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601712.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (17)

#	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

Flagged submissions

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000119488	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	flagged submission Reason: This record appears to be redundant with a more recent record from the same submitter. Notes: SCV000119488 appears to be redundant with SCV000119489.	not provided	not provided	not provided

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000119488

DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE

flagged submission

Reason: This record appears to be redundant with a more recent record from the same submitter.

Notes: SCV000119488 appears to be redundant with SCV000119489.

not provided

Last Updated: Jun 17, 2024

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