ClinVar Miner

Submissions for variant NM_000053.4(ATP7B):c.3317T>A (p.Val1106Asp) (rs775541743)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411980 SCV000487096 likely pathogenic Wilson disease 2016-10-11 criteria provided, single submitter clinical testing
Invitae RCV000411980 SCV001574423 likely pathogenic Wilson disease 2020-10-04 criteria provided, single submitter clinical testing This sequence change replaces valine with aspartic acid at codon 1106 of the ATP7B protein (p.Val1106Asp). The valine residue is moderately conserved and there is a large physicochemical difference between valine and aspartic acid. This variant is present in population databases (rs775541743, ExAC 0.001%). This variant has been observed in individual(s) with Wilson Disease (PMID: 8938442, 20082719). ClinVar contains an entry for this variant (Variation ID: 371498). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ATP7B protein function. Experimental studies have shown that this variant affects ATP7B protein function (PMID: 18203200). This variant disrupts the p.Val1106 amino acid residue in ATP7B. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 14966923, 27022412, 28212618, 26483271, 30702195). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.
Mayo Clinic Laboratories, Mayo Clinic RCV001508707 SCV001715039 likely pathogenic not provided 2019-05-07 criteria provided, single submitter clinical testing PS3, PM2

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