Submissions for variant NM_000277.3(PAH):c.609C>T (p.Cys203=)

gnomAD frequency: 0.00036  dbSNP: rs1801147

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV001082797	SCV001448224	uncertain significance	Phenylketonuria	2020-10-23	reviewed by expert panel	curation	The c.609C>T (p.Cys203=) variant in PAH has not been reported in a patient with PAH deficiency to our knowledge. This variant has a MAF that is too high (0.00473 in gnomAD). A deleterious effect is predicted using HSF, IIEs from Zhang et al, Fas-ESS hexamers, and NNSplice, but Splice AI predicts a benign effect (0). In summary, this variant meets criteria to be classified as uncertain significance for PAH. PAH-specific ACMG/AMP criteria applied: BS1.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001082797	SCV001018718	likely benign	Phenylketonuria	2024-12-24	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001082797	SCV001272689	uncertain significance	Phenylketonuria	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001194127	SCV001363418	likely benign	not specified	2020-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002513934	SCV003683645	likely benign	Inborn genetic diseases	2023-08-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CeGaT Center for Human Genetics Tuebingen	RCV000089005	SCV004810829	likely benign	not provided	2024-03-01	criteria provided, single submitter	clinical testing	PAH: BP4
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089005	SCV000119609	not provided	not provided		no assertion provided	not provided