ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1282C>T (p.Gln428Ter) (rs567261857)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410471 SCV000487095 likely pathogenic Phenylketonuria 2016-10-05 criteria provided, single submitter clinical testing
Invitae RCV000410471 SCV000827177 likely pathogenic Phenylketonuria 2018-02-16 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the PAH gene (p.Gln428*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 24 amino acids of the PAH protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PAH-related disease. ClinVar contains an entry for this variant (Variation ID: 371497). A downstream missense substitution (p.Ala447Asp) has been determined to be pathogenic (PMID: 8659548, 23430918, 9540801). This suggests that the deleted region is critical for PAH protein function and that this variant may also be pathogenic. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000759177 SCV000888343 likely pathogenic not provided 2018-04-26 criteria provided, single submitter clinical testing

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