Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002164 | SCV001160023 | uncertain significance | Wilson disease | 2018-10-09 | criteria provided, single submitter | clinical testing | The ATP7B c.2681C>T; p.Thr894Ile variant, to our knowledge, is not described in the medical literature or in gene-specific databases, and is only observed on 1 allele in the Genome Aggregation Database. The threonine at codon 894 is highly conserved, and computational algorithms (PolyPhen-2, SIFT) predict that this variant is deleterious. However, due to the lack of clinical and functional data regarding this variant, its clinical significance cannot be determined with certainty. |
| Illumina Laboratory Services, |
RCV001002164 | SCV001270800 | uncertain significance | Wilson disease | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
| Invitae | RCV001002164 | SCV001575589 | likely pathogenic | Wilson disease | 2020-10-12 | criteria provided, single submitter | clinical testing | 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. 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. This variant has been observed in individual(s) with Wilsons disease (invitae). ClinVar contains an entry for this variant (Variation ID: 811797). This variant is not present in population databases (ExAC no frequency). This sequence change replaces threonine with isoleucine at codon 894 of the ATP7B protein (p.Thr894Ile). The threonine residue is highly conserved and there is a moderate physicochemical difference between threonine and isoleucine. |
| Genome- |
RCV001002164 | SCV001977155 | uncertain significance | Wilson disease | 2021-08-10 | criteria provided, single submitter | clinical testing | |
| Mayo Clinic Laboratories, |
RCV002261249 | SCV002541586 | uncertain significance | not provided | 2021-12-03 | criteria provided, single submitter | clinical testing |