ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3649_3654del (p.Val1217_Leu1218del) (rs781266802)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000169402 SCV000220801 likely pathogenic Wilson disease 2014-10-15 criteria provided, single submitter literature only
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000169402 SCV001160221 pathogenic Wilson disease 2019-01-11 criteria provided, single submitter clinical testing The ATP7B c.3649_3654delGTTCTG; p.Val1217_Leu1218del variant (rs781266802) also known as 3648del6, is reported in the literature in the compound heterozygous state in multiple individuals affected with Wilson's disease (Ferenci 2005, Folhoffer 2007, Kalinsky 1998, Kemppainen 1997, Loudianos 1998, Petrasek 2007, Thomas 1995, Todorov 2005, Vrabelova 2005, Wright 2009). This variant deletes two amino acid residues leaving the rest of the protein in-frame. This variant is reported in ClinVar (Variation ID: 189015), and is found in the Finnish European population with an allele frequency of 0.014% (3/21,562 alleles) in the Genome Aggregation Database. Based on available information, this variant is considered to be pathogenic. References: Ferenci P et al. Diagnostic value of quantitative hepatic copper determination in patients with Wilson's Disease. Clin Gastroenterol Hepatol. 2005 Aug;3(8):811-8. Folhoffer A et al. Novel mutations of the ATP7B gene among 109 Hungarian patients with Wilson's disease. Eur J Gastroenterol Hepatol. 2007 Feb;19(2):105-11. Kalinsky H et al. Novel ATP7B mutations causing Wilson disease in several Israeli ethnic groups. Hum Mutat. 1998;11(2):145-51. Kemppainen R et al. A homozygous nonsense mutation and a combination of two mutations of the Wilson disease gene in patients with different lysyl oxidase activities in cultured fibroblasts. J Invest Dermatol. 1997 Jan;108(1):35-9. Loudianos G et al. Further delineation of the molecular pathology of Wilson disease in the Mediterranean population. Hum Mutat. 1998;12(2):89-94. Petrasek J et al. Revised King's College score for liver transplantation in adult patients with Wilson's disease. Liver Transpl. 2007 Jan;13(1):55-61. Thomas GR et al. The Wilson disease gene: spectrum of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210-7. Todorov T et al. Spectrum of mutations in the Wilson disease gene (ATP7B) in the Bulgarian population. Clin Genet. 2005 Nov;68(5):474-6. Vrabelova S et al. Mutation analysis of the ATP7B gene and genotype/phenotype correlation in 227 patients with Wilson disease. Mol Genet Metab. 2005 Sep-Oct;86(1-2):277-85. Wright LM et al. Hepatocyte GP73 expression in Wilson disease. J Hepatol. 2009 Sep;51(3):557-64.
Invitae RCV000169402 SCV001221643 likely pathogenic Wilson disease 2020-03-11 criteria provided, single submitter clinical testing This variant, c.3649_3654del, results in the deletion of 2 amino acid(s) of the ATP7B protein (p.Val1217_Leu1218del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs781266802, ExAC 0.003%). This variant has been observed as homozygous or in combination with another ATP7B variant in several individuals affected with Wilson disease (PMID: 19118915, 8980283, 9482578, 17154398, 17272994). This variant is also known as 3648del6 in the literature. ClinVar contains an entry for this variant (Variation ID: 189015). Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. 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.
CeGaT Praxis fuer Humangenetik Tuebingen RCV001091635 SCV001247792 pathogenic not provided 2018-02-01 criteria provided, single submitter clinical testing

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