Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV000375882 | SCV000852094 | pathogenic | Phenylketonuria | 2018-08-10 | reviewed by expert panel | curation | PAH-specific ACMG/AMP criteria applied: PVS1: Frameshift variant; PM2: Extremely low frequency. ExAC MAF: 0.00001.; PP4: Detected in PKU patient in international phase II clinical trial for sapropterin. (PMID:23430918). In summary this variant meets criteria to be classified as pathogenic for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (PVS1, PM2, PP4). |
Eurofins Ntd Llc |
RCV000088953 | SCV000330983 | pathogenic | not provided | 2015-09-04 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000375882 | SCV000696451 | pathogenic | Phenylketonuria | 2016-12-06 | criteria provided, single submitter | clinical testing | Variant summary: The PAH c.503delA (p.Tyr168Serfs) 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.526C>T, p.Arg176X; c.1089delG, p.Lys363fs). One in silico tool predicts a damaging outcome for this variant. This variant was found in 1/121256 control chromosomes at a frequency of 0.0000082, which does not exceed the estimated maximal expected allele frequency of a pathogenic PAH variant (0.0079057). This variant has been reported in two unrelated patients who carry c.1222C>T/p.R408W (pathogenic) in trans (Sarkissian_2011 and one internal sample). In addition, one clinical diagnostic laboratory has classified this variant as pathogenic. Taken together, this variant is classified as pathogenic. |
Labcorp Genetics |
RCV000375882 | SCV003441009 | pathogenic | Phenylketonuria | 2023-04-22 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs199475661, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Tyr168Serfs*27) 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). This premature translational stop signal has been observed in individual(s) with hyperphenylalaninemia (PMID: 24368688). ClinVar contains an entry for this variant (Variation ID: 102705). For these reasons, this variant has been classified as Pathogenic. |
De |
RCV000088953 | SCV000119555 | not provided | not provided | no assertion provided | not provided | ||
Natera, |
RCV000375882 | SCV001455101 | pathogenic | Phenylketonuria | 2020-09-16 | no assertion criteria provided | clinical testing |