NM_000277.3(PAH):c.1A>G (p.Met1Val) AND not provided

Clinical significance:Pathogenic (Last evaluated: Sep 29, 2015)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000088868.3

Allele description [Variation Report for NM_000277.3(PAH):c.1A>G (p.Met1Val)]

NM_000277.3(PAH):c.1A>G (p.Met1Val)

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.1A>G (p.Met1Val)
Other names:
NM_000277.2(PAH):c.1A>G
HGVS:
  • NC_000012.12:g.102917130T>C
  • NG_008690.2:g.46281A>G
  • NM_000277.3:c.1A>GMANE SELECT
  • NM_001354304.2:c.1A>G
  • NP_000268.1:p.Met1Val
  • NP_001341233.1:p.Met1Val
  • NC_000012.11:g.103310908T>C
  • NM_000277.1:c.1A>G
Protein change:
M1V; MET1VAL
Links:
OMIM: 612349.0009; dbSNP: rs62514891
NCBI 1000 Genomes Browser:
rs62514891
Molecular consequence:
  • NM_000277.3:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_001354304.2:c.1A>G - initiatior codon variant - [Sequence Ontology: SO:0001582]
  • NM_000277.3:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.1A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Identifiers:
MedGen: CN517202

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000119464DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTEno assertion providednot providednot providednot provided

SCV000331821EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Pathogenic
(Sep 29, 2015)
germlineclinical testing

Citation Link,

SCV001820869GeneDxno assertion criteria provided
Pathogenic
(Jan 6, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknown1not providednot providednot providednot providedclinical testing
not providednot providednot providednot providednot providednot provided1not providedliterature only

Details of each submission

From DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE, SCV000119464.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providednot providednot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1not providednot provided1not providednot providednot providednot providednot providednot provided

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000331821.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot provided1not providednot providednot provided

From GeneDx, SCV001820869.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Seen in a patient with classic PKU in the presence of a second pathogenic variant in PAH and BH4 responsiveness was unknown (Jeannesson-Thivisol et al., 2015); In vitro functional studies demonstrate a damaging effect of c.1A>G on enzyme activity (John et al., 1992); Initiation codon variant in a gene for which loss-of-function is a known mechanism of disease; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 32668217, 26666653, 1301201, 2574002, 1609797, 17924342, 9634518, 9450897, 9781015)

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 7, 2021

Support Center