ClinVar Miner

Submissions for variant NM_000277.3(PAH):c.1342C>T (p.Leu448Phe)

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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 RCV002600870 SCV002946155 uncertain significance Phenylketonuria 2022-09-27 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 448 of the PAH protein (p.Leu448Phe). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with PAH-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PAH 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 RCV004065583 SCV004998565 uncertain significance Inborn genetic diseases 2024-01-22 criteria provided, single submitter clinical testing The c.1342C>T (p.L448F) alteration is located in exon 13 (coding exon 13) of the PAH gene. This alteration results from a C to T substitution at nucleotide position 1342, causing the leucine (L) at amino acid position 448 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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