Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000277.3(PAH):c.1304A>T (p.Asp435Val)

CA386492936

625291 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5f40c3bc-a96c-4619-bf95-57c324cff700

HGVS expressions

NM_000277.3:c.1304A>T

NM_000277.3(PAH):c.1304A>T (p.Asp435Val)

NC_000012.12:g.102840411T>A

CM000674.2:g.102840411T>A

NC_000012.11:g.103234189T>A

CM000674.1:g.103234189T>A

NC_000012.10:g.101758319T>A

NG_008690.1:g.82192A>T

NG_008690.2:g.123000A>T

NM_000277.1:c.1304A>T

NM_000277.2:c.1304A>T

NM_001354304.1:c.1304A>T

NM_001354304.2:c.1304A>T

ENST00000307000.7:c.1289A>T

ENST00000551114.2:n.966A>T

ENST00000553106.5:c.1304A>T

ENST00000635477.1:n.408A>T

ENST00000635528.1:n.819A>T

Likely Pathogenic

PM2 PM3 PP4_Moderate

PP3

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1304A>T (p.Asp435Val) variant in PAH has been reported in a Uygur patient with moderate PKU (BH4 deficiency ruled out) (PP4_Moderate; PMID: 31355225). This variant was detected with p.Ala434Asp (Likely pathogenic in ClinVar) (PM3; PMID: 31355225). The variant is absent from population databases (PM2). Computational evidence is conflicting. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM2, PM3, PP4_Moderate.

PM2

Variant absent from population databases

PM3

PMID: 31355225 - Patient 108 carried the previously described variant p.Ala434Asp (VarID 102586, LP, 2 submitters), parents were tested - variants confirmed in trans - 1.0 points

PubMed:31332730

PP4_Moderate

PMID: 31355225 - PCR and Sanger sequencing detected D435V in an Uygur patient with moderate PKU (Phe = 360-1200umol/L), BH4 deficiency ruled out

PubMed:31355225

PP3

Variant predicted to be tolerated by SIFT, benign by PolyPhen2, disease causing by MutationTaster, and REVEL = 0.707.

Approved on: 2020-04-10

Published on: 2020-04-10

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.