Submissions for variant NM_000053.4(ATP7B):c.2337G>A (p.Trp779Ter)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000144369	SCV003442157	pathogenic	Wilson disease	2022-02-20	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Trp779*) 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). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 156285). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 16283883). This variant is not present in population databases (gnomAD no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000144369	SCV003845150	pathogenic	Wilson disease	2023-02-24	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.2337G>A (p.Trp779X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 249424 control chromosomes (gnomAD). c.2337G>A has been reported in the literature in multiple individuals affected with Wilson Disease (example: Gromadzka_2005 and Collins_2021). These data indicate that the variant is very likely to be associated with disease. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV003480060	SCV004226668	pathogenic	not provided	2022-03-21	criteria provided, single submitter	clinical testing	PM2, PS4_moderate, PVS1
ClinVar Staff, National Center for Biotechnology Information (NCBI)	RCV000144369	SCV000189436	not provided	Wilson disease		no assertion provided	not provided

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