Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001997260 | SCV002227926 | pathogenic | Wilson disease | 2023-08-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 1448854). This variant is also known as Leu937*. This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 7626145, 25617204). This variant is present in population databases (rs776002066, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Leu936*) in the ATP7B gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). |
| Ambry Genetics | RCV002441097 | SCV002748107 | pathogenic | Inborn genetic diseases | 2017-11-28 | criteria provided, single submitter | clinical testing | The p.L936* pathogenic mutation (also known as c.2807T>A), located in coding exon 12 of the ATP7B gene, results from a T to A substitution at nucleotide position 2807. This changes the amino acid from a leucine to a stop codon within coding exon 12. This mutation has been identified in multiple individuals with Wilson disease, in both the homozygous and compound heterozygous state (Thomas GR et al. Nat. Genet., 1995 Feb;9:210-7; Loudianos G et al. Eur. J. Hum. Genet., 1998 Sep-Oct;6:487-91; Butler P et al. Mol. Genet. Metab., 2001 Mar;72:223-30; Panagiotakaki E et al. Am. J. Med. Genet. A, 2004 Dec;131:168-73; Lepori MB et al. Mol. Cell. Probes, 2012 Aug;26:147-50; Simsek Papur O et al. Eur J Med Genet, 2013 Apr;56:175-9). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Baylor Genetics | RCV001997260 | SCV004216366 | pathogenic | Wilson disease | 2023-08-05 | criteria provided, single submitter | clinical testing | |
| Laboratory for Molecular Medicine, |
RCV001997260 | SCV004848791 | pathogenic | Wilson disease | 2022-11-03 | criteria provided, single submitter | clinical testing | The p.Leu936X variant in ATP7B has been reported in at least 3 individuals with Wilson disease (at least 1 compound heterozygous)(Thomas 1995 PMID: 7626145, Ivanova 2015 PMID: 25617204). This variant has been reported in ClinVar (Variation ID 1448854) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 936, which is predicted to lead to a truncated or absent protein. Loss of function of the ATP7B gene is an established disease mechanism in autosomal recessive Wilson disease. In summary, , this variant meets criteria to be classified as pathogenic for autosomal recessive Wilson disease. ACMG/AMP Criteria applied: PVS1, PM2_Supporting, PM3_Supporting. |
| Fulgent Genetics, |
RCV001997260 | SCV005636158 | pathogenic | Wilson disease | 2023-12-28 | criteria provided, single submitter | clinical testing |