ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.441+3G>C (rs62508642)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ClinGen PAH Variant Curation Expert Panel RCV000665892 SCV001250557 pathogenic Phenylketonuria 2019-10-18 reviewed by expert panel curation This c.441+3G>C (IVS4+3G>C) variant was documented at least 7 times in patients with PAH deficiency with a pathogenic or likely pathogenic variant in trans (PMID: 28982351, 5894915, 30050108). This variant was also documented in two patients homozygous for the c.441+3G>C variant, one diagnosed with mild PKU and one diagnosed with classic PKU (PMID: 30050108). This variant was documented 12 times in patients with PAH deficiency; DHPR activity, biopterin and/or pteridine analysis was performed to rule out other causes of hyperphenylalaninemia (PMID: 26503515, 16256386, 23932990). This variant is absent from the population databases ExAC and gnomAD. In summary, this variant meets criteria to be classified as pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PM3_very strong, PM2, PP4_moderate.
Counsyl RCV000665892 SCV000790088 likely pathogenic Phenylketonuria 2017-03-15 criteria provided, single submitter clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000088920 SCV000119518 not provided not provided no assertion provided not provided

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