Description
Variant summary: The PAH c.618C>A (p.Tyr206X) variant results in a premature termination codon, predicted to cause a truncated or absent PAH 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 (e.g. c.727C>T, p.Arg243X; c.1055delG, p.Gly352fsX48; c.1089delG, p.Lys363fsX37). One in silico tool predicts a damaging outcome for this variant. One functional study confirmed that the variant leads to a nonsense mutation that caused significant reduction in mutant transcript levels possibly through activation of nonsense mediated decay (Bashyam 2014). This variant was found in 1/121330 control chromosomes at a frequency of 0.00082%, which does not exceed the estimated maximal expected allele frequency of a pathogenic PAH variant (0.79057%). The variant was reported in the literature in multiple patients with PKU (Song 2006, Bashyam 2014, Li 2015, Acosta 2001). Taken together, this variant is classified as pathogenic.
# | Sample | Method | Observation |
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Origin | Affected | Number tested | Tissue | Purpose | Method | Individuals | Allele frequency | Families | Co-occurrences |
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1 | germline | unknown | not provided | not provided | not provided | | not provided | not provided | not provided | not provided |