Submissions for variant NM_000277.3(PAH):c.352+1G>A

dbSNP: rs199475684

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV002509218	SCV002818526	likely pathogenic	Phenylketonuria	2022-12-09	reviewed by expert panel	curation	This canonical PAH variant c.352+1G>A is predicted to result in nonsense mediated decay. This variant was absent in population databases. This variant has been reported in the literature (PMID: 20140859), but is not available for review. In summary, this variant meets criteria to be classified as likely pathogenic for PAH. PAH-specific ACMG/AMP criteria applied: PVS1,PM2.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002509218	SCV003441010	pathogenic	Phenylketonuria	2022-09-14	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 102653). Disruption of this splice site has been observed in individual(s) with hyperphenylalaninemia (PMID: 32668217). This variant is not present in population databases (gnomAD no frequency). This sequence change affects a donor splice site in intron 3 of the PAH gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PAH are known to be pathogenic (PMID: 1301187, 9634518).
Baylor Genetics	RCV002509218	SCV004209634	pathogenic	Phenylketonuria	2023-07-20	criteria provided, single submitter	clinical testing
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088900	SCV000119498	not provided	not provided		no assertion provided	not provided