Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001022964 | SCV001184765 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-08-12 | criteria provided, single submitter | clinical testing | The p.D158N variant (also known as c.472G>A), located in coding exon 1 of the CDKN1B gene, results from a G to A substitution at nucleotide position 472. The aspartic acid at codon 158 is replaced by asparagine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, asparagine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Invitae | RCV001036066 | SCV001199413 | uncertain significance | Multiple endocrine neoplasia type 4 | 2022-06-04 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with CDKN1B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 158 of the CDKN1B protein (p.Asp158Asn). ClinVar contains an entry for this variant (Variation ID: 825130). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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. |