ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1282C>G (p.Gln428Glu)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV002676879 SCV002990484 uncertain significance Phenylketonuria 2021-12-02 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 428 of the PAH protein (p.Gln428Glu). This variant is present in population databases (rs567261857, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with PAH-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics RCV002695260 SCV003588842 uncertain significance Inborn genetic diseases 2021-11-12 criteria provided, single submitter clinical testing The c.1282C>G (p.Q428E) alteration is located in exon 12 (coding exon 12) of the PAH gene. This alteration results from a C to G substitution at nucleotide position 1282, causing the glutamine (Q) at amino acid position 428 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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