NM_000277.3(PAH):c.638T>C (p.Leu213Pro) AND not provided

Germline classification:: Pathogenic (4 submissions)
Last evaluated:: Aug 26, 2023
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:: RCV000078527.36

Allele description [Variation Report for NM_000277.3(PAH):c.638T>C (p.Leu213Pro)]

NM_000277.3(PAH):c.638T>C (p.Leu213Pro)

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.638T>C (p.Leu213Pro)

Other names:

p.L213P:CTT>CCT; NM_000277.1(PAH):c.638T>C

HGVS:

NC_000012.12:g.102855204A>G
NG_008690.2:g.108207T>C
NM_000277.3:c.638T>CMANE SELECT
NM_001354304.2:c.638T>C
NP_000268.1:p.Leu213Pro
NP_000268.1:p.Leu213Pro
NP_001341233.1:p.Leu213Pro
NC_000012.11:g.103248982A>G
NM_000277.1:c.638T>C
P00439:p.Leu213Pro

Protein change:

L213P

Links:

UniProtKB: P00439#VAR_000930; dbSNP: rs62516109

NCBI 1000 Genomes Browser:

rs62516109

Molecular consequence:

NM_000277.3:c.638T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001354304.2:c.638T>C - missense variant - [Sequence Ontology: SO:0001583]

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
SCV000110383	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Pathogenic (Aug 14, 2012)	germline	clinical testing	Citation Link,
SCV000119623	DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	no classification provided	not provided	not provided	not provided
SCV000239064	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Pathogenic (Aug 26, 2023)	germline	clinical testing	Citation Link,
SCV001249186	CeGaT Center for Human Genetics Tuebingen	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	Pathogenic (Jul 1, 2019)	germline	clinical testing	Citation Link

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
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	1	not provided	literature only
not provided	germline	yes	1	not provided	not provided	not provided	not provided	clinical testing

Details of each submission

From Eurofins Ntd Llc (ga), SCV000110383.8

#	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, SCV000119623.1

#	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, SCV000239064.7

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

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Tetrahydrobiopterin (BH4) responsiveness is inconsistent (Sarkissian et al., 2012; Djordjevic et al., 2013); This variant is associated with the following publications: (PMID: 9521426, 22112818, 23764561, 25750018, 23430918, 8659548, 23430547, 26666653, 19292873, 32668217, 35405047)

#	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 CeGaT Center for Human Genetics Tuebingen, SCV001249186.26

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

Last Updated: Nov 3, 2024

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