Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463157 | SCV000541776 | uncertain significance | Multiple endocrine neoplasia type 4 | 2024-01-18 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 42 of the CDKN1B protein (p.Thr42Ile). This variant is present in population databases (rs200422211, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 404278). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. 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 | RCV001010623 | SCV001170848 | benign | Hereditary cancer-predisposing syndrome | 2023-06-15 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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. |
Sema4, |
RCV001010623 | SCV002535469 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-24 | criteria provided, single submitter | curation | |
Gene |
RCV002461185 | SCV002757231 | uncertain significance | not provided | 2022-11-21 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 26603463, 30065701, 22722193) |
St. |
RCV000463157 | SCV004171506 | uncertain significance | Multiple endocrine neoplasia type 4 | 2023-10-20 | criteria provided, single submitter | clinical testing | The CDKN1B c.125C>T (p.Thr42Ile) missense change has a maximum subpopulation frequency of 0.029% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with multiple endocrine neoplasia type 4. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |