ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.960G>C (p.Lys320Asn) (rs199475615)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000089174 SCV000329865 pathogenic not provided 2016-10-03 criteria provided, single submitter clinical testing The K320N variant has previously been reported in association with mild PKU and hyperphenylalaninemia and is classified as a BH4 responsive variant (Lücke et al., 2003; Steinfeld et al., 2004; Blau et al., 2004).
Invitae RCV000666332 SCV001391599 pathogenic Phenylketonuria 2019-05-29 criteria provided, single submitter clinical testing This sequence change replaces lysine with asparagine at codon 320 of the PAH protein (p.Lys320Asn). The lysine residue is highly conserved and there is a moderate physicochemical difference between lysine and asparagine. This variant is present in population databases (rs199475615, ExAC 0.001%). This variant has been observed in combination with another PAH variant in several individuals affected with PAH-related conditions (PMID: 24350308, 23764561, 12655554, 8659548, 12655553, 11678552). ClinVar contains an entry for this variant (Variation ID: 102910). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). For these reasons, this variant has been classified as Pathogenic.
DeBelle Laboratory for Biochemical Genetics, MUHC/MCH RESEARCH INSTITUTE RCV000089174 SCV000119789 not provided not provided no assertion provided not provided
Counsyl RCV000666332 SCV000790605 likely pathogenic Phenylketonuria 2017-10-09 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.