Submissions for variant NM_000053.4(ATP7B):c.4051C>T (p.Gln1351Ter)

dbSNP: rs786204578

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000726684	SCV000702098	pathogenic	not provided	2016-10-04	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000726684	SCV000883429	pathogenic	not provided	2017-12-01	criteria provided, single submitter	clinical testing	The ATP7B c.4051C>T, p.Gln1351Ter variant (rs786204578) has been reported in multiple individuals with Wilson's disease (Folhoffer 2007, Genschel 2000, Gromadzka 2005, Moller 2011, Vrabelova 2005). It is listed in ClinVar (Variation ID: 188947), and observed once in the Genome Aggregation Database general population database (1/242182 alleles). The variant introduces a premature termination codon, and is predicted to result in a truncated protein or an absent transcript. Based on the above information, the variant is classified as pathogenic. References: Folhoffer A et al. Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease. Eur J Gastroenterol Hepatol. 2007; 19(2):105-11. Genschel J et al. Three novel mutations (P760L, L1305P, Q1351Stop) causing Wilson disease. Hum Mutat. 2001; 17(2):156. Gromadzka G et al. Frameshift and nonsense mutations in the gene for ATPase7B are associated with severe impairment of copper metabolism and with an early clinical manifestation of Wilson's disease. Clin Genet. 2005; 68(6):524-32. Moller L et al. Clinical presentation and mutations in Danish patients with Wilson disease. Eur J Hum Genet. 2011; 19(9):935-41. Vrabelova S et al. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab. 2005; 86(1-2):277-85.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000169321	SCV000918590	pathogenic	Wilson disease	2017-10-06	criteria provided, single submitter	clinical testing	Variant summary: The ATP7B c.4051C>T (p.Gln1351X) variant results in a premature termination codon, predicted to cause a truncated or absent ATP7B protein due to nonsense mediated decay, which are commonly known mechanisms for disease. This variant was found in 1/242182 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic ATP7B variant (0.0054006). Multiple publications cite the variant in compound heterozygote and homozygote affected individuals. A clinical diagnostic laboratory classified this variant as likely pathogenic. Taken together, this variant is classified as pathogenic.
Invitae	RCV000169321	SCV001232297	pathogenic	Wilson disease	2023-12-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1351*) 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). This variant is present in population databases (rs786204578, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 11180609, 16283883, 26799313). ClinVar contains an entry for this variant (Variation ID: 188947). For these reasons, this variant has been classified as Pathogenic.
Genome-Nilou Lab	RCV000169321	SCV001977214	pathogenic	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000169321	SCV002798005	pathogenic	Wilson disease	2022-05-09	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000169321	SCV004216342	pathogenic	Wilson disease	2023-09-05	criteria provided, single submitter	clinical testing
Mayo Clinic Laboratories, Mayo Clinic	RCV000726684	SCV004226639	pathogenic	not provided	2023-06-14	criteria provided, single submitter	clinical testing	PP4, PM2, PM3, PS4_moderate, PVS1_strong
Counsyl	RCV000169321	SCV000220652	pathogenic	Wilson disease	2016-09-09	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000169321	SCV001455572	pathogenic	Wilson disease	2020-09-16	no assertion criteria provided	clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas	RCV000169321	SCV004101121	pathogenic	Wilson disease	2023-11-02	no assertion criteria provided	clinical testing