ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.169-13T>G (rs62507341)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000088853 SCV000617704 pathogenic not provided 2017-08-10 criteria provided, single submitter clinical testing The c.169-13 T>G variant has been reported previously in multiple patients with hyperphenylalaninemia and with classic PKU when observed with other variants known to be associated with a classic PKU phenotype (Bosco et al. 1998; Kasnauskiene et al. 2003). The c.169-13 T>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Furthermore, in silico analyses, including splice predictors and evolutionary conservation, support that the c.169-13 T>G variant has a deleterious effect. In summary, we interpret c.169-13 T>G to be pathogenic.
Illumina Clinical Services Laboratory,Illumina RCV000778351 SCV000914559 pathogenic Phenylketonuria 2018-12-06 criteria provided, single submitter clinical testing The PAH c.169-13T>G intron variant has been reported in five studies and is found in a total of seven individuals with phenylalanine hydroxylase deficiency including in six in a compound heterozygous state and in one in a heterozygous state where the second variant could not be identified (Bosco et al. 1998; Kasnauskiene et al. 2003; Kasnauskiene et al. 2008; Zurflüh et al. 2008; Esfahani et al. 2018). Control data are unavailable for this variant which is reported at a frequency of 0.000009 in the European (non-Finnish) population of the Genome Aggregation Database. This is based on one allele only in a region with good coverage, suggesting that this is a rare variant. Authors predict this variant may activate a cryptic splice site, but no supporting evidence is provided (Bosco et al. 1998). Based on the clinical evidence, the c.169-13T>G variant is classified as pathogenic for phenylalanine hydroxylase deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088853 SCV000119448 not provided not provided no assertion provided not provided

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