Submissions for variant NM_000053.4(ATP7B):c.3895del (p.Ile1300fs)

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Total submissions: 3

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001174880	SCV001338288	pathogenic	Wilson disease	2020-02-09	criteria provided, single submitter	clinical testing	Variant summary: ATP7B c.3895delC (p.Ile1300SerfsX30) 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 249420 control chromosomes. c.3895delC has been reported in the literature in at-least two individuals affected with Wilson Disease and has been subsequently cited by other studies (example, Santosh_2006, Nicastro_2010, Gupta_2007, Mathur_2015, Liu_2018). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Genome-Nilou Lab	RCV001174880	SCV001977225	pathogenic	Wilson disease	2021-08-10	criteria provided, single submitter	clinical testing
Invitae	RCV001174880	SCV002247001	pathogenic	Wilson disease	2021-10-16	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 917707). This premature translational stop signal has been observed in individual(s) with Wilson disease (PMID: 17264425). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile1300Serfs*30) 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).

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