NM_000277.3(PAH):c.307G>T (p.Gly103Cys) AND not specified

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 21, 2024
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:
RCV004689843.1

Allele description [Variation Report for NM_000277.3(PAH):c.307G>T (p.Gly103Cys)]

NM_000277.3(PAH):c.307G>T (p.Gly103Cys)

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.307G>T (p.Gly103Cys)
Other names:
NM_000277.2(PAH):c.307G>T; p.Gly103Cys
HGVS:
  • NC_000012.12:g.102894780C>A
  • NG_008690.2:g.68631G>T
  • NM_000277.3:c.307G>TMANE SELECT
  • NM_001354304.2:c.307G>T
  • NP_000268.1:p.Gly103Cys
  • NP_001341233.1:p.Gly103Cys
  • NC_000012.11:g.103288558C>A
  • NM_000277.1:c.307G>T
Protein change:
G103C
Links:
dbSNP: rs752792040
NCBI 1000 Genomes Browser:
rs752792040
Molecular consequence:
  • NM_000277.3:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001354304.2:c.307G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005185122Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(May 21, 2024) 		germlineclinical testing

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness.

Ho G, Alexander I, Bhattacharya K, Dennison B, Ellaway C, Thompson S, Wilcken B, Christodoulou J.

JIMD Rep. 2014;14:55-65. doi: 10.1007/8904_2013_284. Epub 2013 Dec 25.

PubMed [citation]
PMID:
24368688
PMCID:
PMC4213336

Mutations in the phenylalanine hydroxylase gene identified in 95 patients with phenylketonuria using novel systems of mutation scanning and specific genotyping based upon thermal melt profiles.

Dobrowolski SF, Ellingson C, Coyne T, Grey J, Martin R, Naylor EW, Koch R, Levy HL.

Mol Genet Metab. 2007 Jul;91(3):218-27. Epub 2007 May 14.

PubMed [citation]
PMID:
17502162
See all PubMed Citations (3)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005185122.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Variant summary: PAH c.307G>T (p.Gly103Cys) results in a non-conservative amino acid change located in the ACT domain (IPR002912) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The frequency data for this variant in gnomAD is considered unreliable, as metrics indicate poor data quality at this position. c.307G>T has been reported in the literature in compound heterozygous individuals affected with Phenylalanine Hydroxylase Deficiency (Phenylketonuria) (e.g. Dobrowolski_2007, Ho_2014). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 17502162, 32668217, 24368688). ClinVar contains an entry for this variant (Variation ID: 553638). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.

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

Last Updated: Sep 29, 2024