Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000674358 | SCV004222631 | pathogenic | Phenylketonuria | 2023-10-15 | reviewed by expert panel | curation | The c.910C>T (p.Gln304Ter) variant in PAH has been reported in at least 1 individual with PKU however without indication of the genotype (BH4 deficiency not ruled out) (PMID: 23357515) . This variant occurs in exon 8 of 13 of PAH, a gene where loss of function is a known disease mechanism, and is predicted to result in a truncated protein (with truncation of >10% of the encoded protein) or mRNA subject to nonsense-mediated decay. The c.910C>T variant is absent from gnomAD and the ESP population databases. Based on available information, this variant is considered to be pathogenic. PAH-specific ACMG/AMP criteria applied: PVS1, PM2_supporting, PP4. |
Counsyl | RCV000674358 | SCV000799682 | likely pathogenic | Phenylketonuria | 2018-05-01 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000674358 | SCV001372269 | pathogenic | Phenylketonuria | 2020-06-28 | criteria provided, single submitter | clinical testing | Variant summary: PAH c.910C>T (p.Gln304X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250994 control chromosomes. c.910C>T has been reported in the literature in at-least one individual affected with Phenylalanine Hydroxylase Deficiency, in locus specific database and subsequently cited by others (example, Reblova_2013, Wettstein_2015, Yan_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Baylor Genetics | RCV000674358 | SCV004209610 | pathogenic | Phenylketonuria | 2023-08-25 | criteria provided, single submitter | clinical testing |