Submissions for variant NM_000053.4(ATP7B):c.3912G>T (p.Leu1304Phe)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003062591	SCV003442220	likely pathogenic	Wilson disease	2022-09-20	criteria provided, single submitter	clinical testing	In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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 expected to disrupt ATP7B protein function. This missense change has been observed in individual(s) with Wilson disease (PMID: 21610751; Invitae). This variant is present in population databases (rs748644391, gnomAD 0.003%). This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 1304 of the ATP7B protein (p.Leu1304Phe).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV003062591	SCV005199912	likely pathogenic	Wilson disease	2024-08-23	criteria provided, single submitter	clinical testing	variant in homozygous state