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]

Variant: NM_000277.3(PAH):c.1043_1053del (p.Leu348fs)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA229297

102489 (ClinVar)

Gene: PAH

Condition: phenylketonuria

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 9f581382-e0ca-437f-9223-3cc676ad3184

Approved on: 2020-10-30

Published on: 2020-10-30

HGVS expressions

NM_000277.3:c.1043_1053del

NM_000277.3(PAH):c.1043_1053del (p.Leu348fs)

NC_000012.12:g.102844348_102844358del

CM000674.2:g.102844348_102844358del

NC_000012.11:g.103238126_103238136del

CM000674.1:g.103238126_103238136del

NC_000012.10:g.101762256_101762266del

NG_008690.1:g.78245_78255del

NG_008690.2:g.119053_119063del

NM_000277.1:c.1043_1053del

NM_000277.2:c.1043_1053del

NM_001354304.1:c.1043_1053del

NM_001354304.2:c.1043_1053del

ENST00000307000.7:c.1028_1038del

ENST00000549247.6:n.802_812del

ENST00000551114.2:n.705_715del

ENST00000553106.5:c.1043_1053del

ENST00000635477.1:n.147_157del

ENST00000635528.1:n.558_568del

Pathogenic

PVS1 PP4 PM2 PM3_Supporting

Evidence Links 2

Expert Panel

Phenylketonuria VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Phenylketonuria VCEP

The c.1043_1053del (p.Leu348fs) variant in PAH has been reported in 1 female patient with classic PKU, serum Phe = 2600 umol/L; BH4 deficiency not excluded (PP4_Moderate). This variant was detected with R408W, reported as Pathogenic in ClinVar, phase not confirmed (0.5 points; PM3_Supporting). This frameshift variant is predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons) (PVS1), and is absent from population databases (PM2). In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4, PM3_Supporting.

PVS1

Frameshift variant, predicted to undergo NMD, not located in last exon or last 50bp of preliminary exon. Coding exon number 10 out of 13 coding exons (10 out of total exons).

PP4

PMID: 11328945 - L348fs dected in 1 female patient with classic PKU, serum Phe = 2600 umol/L; BH4 deficiency not excluded

PubMed:11328945

PubMed:9781015

PM2

Variant absent from population databases.

PM3_Supporting

PMID: 11328945 - L348fs detected with R408W, reported as Pathogenic in ClinVar (VarID:577, 21 submitters), phase not confirmed - 0.5 points

Curation History

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