Submissions for variant NM_000277.3(PAH):c.820A>G (p.Lys274Glu)

gnomAD frequency: 0.00496  dbSNP: rs142934616

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen PAH Variant Curation Expert Panel	RCV000148723	SCV000852105	likely benign	Phenylketonuria	2018-08-10	reviewed by expert panel	curation	PAH-specific ACMG/AMP criteria applied: BS1: MAF= 0.01815 in 1000G. 2 homozygotes in ExAC, 1 homozygote in 1000G.; BS3_Supporting: Enzyme activity of K274E is indistinguishable from that of the wild-type protein. Detailed kinetic analyses of PAH expressed in E. coli showed that the K274E mutant protein has kinetic properties similar to that of the wild-type protein. (PMID:11461196). In summary this variant meets criteria to be classified as likely benign for phenylketonuria in an autosomal recessive manner based on the ACMG/AMP criteria applied as specified by the PAH Expert Panel: (BS1, BS3_Supporting).
Counsyl	RCV000148723	SCV000220150	likely benign	Phenylketonuria	2014-03-19	criteria provided, single submitter	literature only
Labcorp Genetics (formerly Invitae), Labcorp	RCV000148723	SCV001014240	benign	Phenylketonuria	2024-02-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000148723	SCV001138800	benign	Phenylketonuria	2019-05-28	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000089112	SCV005216785	likely benign	not provided		criteria provided, single submitter	not provided
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE	RCV000089112	SCV000119719	not provided	not provided		no assertion provided	not provided
CSER _CC_NCGL, University of Washington	RCV000148723	SCV000190455	likely benign	Phenylketonuria	2014-06-01	no assertion criteria provided	research
Natera, Inc.	RCV000148723	SCV001455413	benign	Phenylketonuria	2020-04-17	no assertion criteria provided	clinical testing