Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000664486 | SCV002032223 | likely pathogenic | Phenylketonuria | 2020-06-01 | reviewed by expert panel | curation | The c.668A>T (p.Asn223Ile) variant in PAH has been reported in 2 individuals with PKU and MHP (BH4 deficiency excluded). (PMID: 30050108). This variant has extremely low frequency in gnomAD (MAF=0.0001307). This variant was detected with in trans with p.Y166* (PMID: 30050108). Computational evidence supports a deleterious effect. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PP4_Moderate, PM2, PM3, PP3. |
Counsyl | RCV000664486 | SCV000788452 | uncertain significance | Phenylketonuria | 2018-02-15 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003420168 | SCV004106534 | likely pathogenic | PAH-related condition | 2022-09-30 | criteria provided, single submitter | clinical testing | The PAH c.668A>T variant is predicted to result in the amino acid substitution p.Asn223Ile. This variant has been reported in at least two individuals with phenylketonuria, one of which was compound heterozygous with a null allele (Li et al. 2015. PubMed ID: 26503515; Li at al. 2018. PubMed ID: 30050108). This variant is reported in 0.013% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-103248952-T-A). It is classified as Likely Pathogenic in ClinVar by a ClinGen expert panel (https://www.ncbi.nlm.nih.gov/clinvar/variation/549912/). Taken together, we interpret this variant to be likely pathogenic. |