ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.703C>T (p.Gln235Ter)

dbSNP: rs1237792711
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV002260490 SCV002540131 pathogenic Phenylketonuria 2020-12-08 reviewed by expert panel curation The NM_000277.3(PAH):c.703C>T (p.Gln235Ter) nonsense variant occurs in exon 6 of 13 and is predicted to result in NMD. It has been reported in one classic PKU patient (http://www.fedoa.unina.it/9088/1/TESI%20DOTTORATO%20ALESSIA%20PALMIERI.pdf) and is found at an extremely low allele frequency in gnomAD (MAF of 0.00006152 in the African/African-American population). In summary, this variant meets criteria to be classified as Pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1, PM2, PP4.
Labcorp Genetics (formerly Invitae), Labcorp RCV002260490 SCV003441286 pathogenic Phenylketonuria 2023-09-06 criteria provided, single submitter clinical testing This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia (PMID: 23352163). This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Gln235*) in the PAH gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518). ClinVar contains an entry for this variant (Variation ID: 1693231). For these reasons, this variant has been classified as Pathogenic.

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