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

dbSNP: rs62508642

Total submissions: 4

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
Baylor Genetics	RCV000665892	SCV004201959	pathogenic	Phenylketonuria	2022-11-15	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