ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.168_168+1delinsAA

dbSNP: rs786204457
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000169094 SCV001146712 likely pathogenic Phenylketonuria 2019-08-25 reviewed by expert panel curation The c.168_168+1delGGinsAA variant has been identified in at least 6 probands with classic PKU (PMIDs: 1301942, 8825928). It has been detected in the homozygous form (PMID: 1301942) as well as in trans with the pathogenic variant R408W (PMID: 8825928). This variant is absent from 1000G, ESP, and gnomAD databases. This variant results in a broken donor splice site, expected to result in the in-frame deletion of exon 2. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM3_Strong, PVS1_Moderate, PM2, PP4.
Counsyl RCV000169094 SCV000220282 likely pathogenic Phenylketonuria 2014-04-29 criteria provided, single submitter literature only
Fulgent Genetics, Fulgent Genetics RCV000169094 SCV002788765 pathogenic Phenylketonuria 2022-01-14 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000169094 SCV004237397 pathogenic Phenylketonuria 2023-04-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000169094 SCV004461300 pathogenic Phenylketonuria 2024-05-22 criteria provided, single submitter clinical testing This variant results in the deletion of part of exon 2 (c.168_168+1delinsAA) of the PAH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has been observed in individuals with phenylketonuria (PMID: 1301942, 8825928). This variant is also known as IVS2nt1. ClinVar contains an entry for this variant (Variation ID: 188771). For these reasons, this variant has been classified as Pathogenic.

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