Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Counsyl | RCV000169268 | SCV000220568 | likely pathogenic | Wilson disease | 2014-08-01 | criteria provided, single submitter | literature only | |
Invitae | RCV000169268 | SCV001373016 | pathogenic | Wilson disease | 2022-11-19 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects ATP7B function (PMID: 19937698). 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. ClinVar contains an entry for this variant (Variation ID: 188908). This missense change has been observed in individual(s) with Wilson disease (PMID: 10544227, 21610751, 24094725). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces serine, which is neutral and polar, with phenylalanine, which is neutral and non-polar, at codon 1363 of the ATP7B protein (p.Ser1363Phe). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000169268 | SCV001572524 | pathogenic | Wilson disease | 2021-04-14 | criteria provided, single submitter | clinical testing | Variant summary: ATP7B c.4088C>T (p.Ser1363Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 246976 control chromosomes (gnomAD). c.4088C>T (p.Ser1363Phe) has been reported in the literature in multiple homozygous and compound heterozygous individuals affected with Wilson Disease (e.g. Loudianos_1999, Moller_2011, Mukherjee_2014). These data indicate that the variant is very likely to be associated with disease. Experimental evidence demonstrated the variant affects protein function (e.g. van den Berghe_2009). A ClinVar submitter (evaluation after 2014) cites the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |
Genome- |
RCV000169268 | SCV001977212 | pathogenic | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV000169268 | SCV004216427 | pathogenic | Wilson disease | 2023-05-04 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV003480071 | SCV004226637 | pathogenic | not provided | 2022-08-23 | criteria provided, single submitter | clinical testing | PP3, PP4, PM2, PM3_strong, PS4_moderate |
Revvity Omics, |
RCV000169268 | SCV004238413 | pathogenic | Wilson disease | 2023-06-12 | criteria provided, single submitter | clinical testing |