ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.4051C>T (p.Gln1351Ter) (rs786204578)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics 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.
Integrated Genetics/Laboratory Corporation of America 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 2019-12-11 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. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with Wilson disease (PMID: 11180609, 16283883, 26799313). ClinVar contains an entry for this variant (Variation ID: 188947). Loss-of-function variants in ATP7B are known to be pathogenic (PMID: 10441329, 16283883). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000169321 SCV000220652 pathogenic Wilson disease 2016-09-09 no assertion criteria provided clinical testing

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