Submissions for variant NM_000277.3(PAH):c.1199+17G>A

gnomAD frequency: 0.00001  dbSNP: rs62508613

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000088789	SCV000330982	likely pathogenic	not provided	2016-04-29	criteria provided, single submitter	clinical testing
Unidade de Bioquimica Genetica, Centro Hospitalar do Porto	RCV000316500	SCV000616624	likely pathogenic	Phenylketonuria	2017-11-10	criteria provided, single submitter	clinical testing	The variant was observed in four patients, two with a diagnosis of phenylketonuria (PKU) and the other two with a diagnosis of mild hyperphenylalaninemia (MHP). In the two PKU patients, the variant was found in compound heterozygosity with IVS10-11G>A (c.1066-11G>A), in intron 10, and c.250G>T (p.D84Y), in exon 3. Meanwhile, in the two MHP patients, it was found with IVS2+5G>C (c.168+5G>C), in intron 2, and c.754C>T (p.R252W), in exon 7. In silico analysis in Human Splicing Finder showed that it activates an intronic cryptic acceptor site, which potentially alters splicing.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000316500	SCV000629176	pathogenic	Phenylketonuria	2024-12-19	criteria provided, single submitter	clinical testing	This sequence change falls in intron 11 of the PAH gene. It does not directly change the encoded amino acid sequence of the PAH protein. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individual(s) with hyperphenylalaninemia (PMID: 11139255, 30829006; internal data). This variant is also known as IVS11+17G>A. ClinVar contains an entry for this variant (Variation ID: 102555). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. For these reasons, this variant has been classified as Pathogenic.
GeneDx	RCV000088789	SCV000709881	pathogenic	not provided	2023-10-19	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 11139255, 31589614, 32668217, 30829006, 29684050)
Counsyl	RCV000316500	SCV000799396	likely pathogenic	Phenylketonuria	2018-04-17	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000316500	SCV001163712	pathogenic	Phenylketonuria	2024-03-11	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000088789	SCV004811861	pathogenic	not provided	2024-03-01	criteria provided, single submitter	clinical testing	PAH: PM3:Very Strong, PM2, PS3:Supporting
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000088789	SCV000119376	not provided	not provided		no assertion provided	not provided