Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000471822 | SCV000553923 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-01-21 | criteria provided, single submitter | clinical testing | This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 470 of the BAP1 protein (p.Gly470Arg). This variant is present in population databases (rs576538858, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 133663). 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 not expected to disrupt BAP1 protein function with a negative predictive value of 80%. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Ambry Genetics | RCV000574998 | SCV000672757 | likely benign | Hereditary cancer-predisposing syndrome | 2023-04-04 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Mendelics | RCV003492520 | SCV000838038 | likely benign | Hereditary cancer | 2024-01-23 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000574998 | SCV000902856 | likely benign | Hereditary cancer-predisposing syndrome | 2021-08-11 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001527719 | SCV001738846 | uncertain significance | not provided | 2022-06-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with thyroid cancer and healthy individuals under age 50 undergoing whole genome sequencing (Bodian 2014, Yehia 2018); This variant is associated with the following publications: (PMID: 30480620, 24728327, 29684080) |
Sema4, |
RCV000574998 | SCV002537259 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-31 | criteria provided, single submitter | curation | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001527719 | SCV004220464 | uncertain significance | not provided | 2023-09-08 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in an individual with thyroid cancer (PMID: 29684080 (2018)), and in healthy individuals under the age of 50 (PMID: 24728327 (2014)). It has also been reported as a somatic variant in an individual with uveal melanoma (PMID: 30480620 (2019)). The frequency of this variant in the general population, 0.00023 (8/34582 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
ITMI | RCV000120191 | SCV000084337 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Genome |
RCV000471822 | SCV004228670 | not provided | BAP1-related tumor predisposition syndrome | no assertion provided | phenotyping only | Variant interpreted as Uncertain significance and reported on 10-22-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information. |