Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000162207 | SCV001395064 | uncertain significance | Multiple endocrine neoplasia type 4 | 2023-11-08 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 69 of the CDKN1B protein (p.Pro69Leu). This variant is present in population databases (rs777354267, gnomAD 0.0009%). This missense change has been observed in individual(s) with multiple endocrine tumors, sarcoma, pituitary adenoma and hyperparathyroidism (PMID: 20824794, 29625052, 32386678). ClinVar contains an entry for this variant (Variation ID: 183393). 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 disruptive. Experimental studies have shown that this missense change affects CDKN1B function (PMID: 20824794). 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 | RCV002415708 | SCV002727686 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-12-14 | criteria provided, single submitter | clinical testing | The p.P69L variant (also known as c.206C>T), located in coding exon 1 of the CDKN1B gene, results from a C to T substitution at nucleotide position 206. The proline at codon 69 is replaced by leucine, an amino acid with similar properties. This variant has been reported in an individual with papillary thyroid carcinoma, nonfunctioning pituitary microadenoma, as well as other comorbidities; in vitro fuctional studies showed this variant resulted in consistently reduced expression and slightly faster degradation compared to wild type (Molatore S et al. Hum. Mutat., 2010 Nov;31:E1825-35). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Revvity Omics, |
RCV000162207 | SCV003823115 | uncertain significance | Multiple endocrine neoplasia type 4 | 2023-04-19 | criteria provided, single submitter | clinical testing | |
| KCCC/NGS Laboratory, |
RCV000162207 | SCV005045519 | uncertain significance | Multiple endocrine neoplasia type 4 | 2024-05-27 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 69 of the CDKN1B protein (p.Pro69Leu). This variant is present in population databases (rs777354267, gnomAD 0.0009%). This missense change has been observed in individual(s) with multiple endocrine tumors, sarcoma, pituitary adenoma and hyperparathyroidism (PMID: 20824794, 29625052, 32386678). ClinVar contains an entry for this variant (Variation ID: 183393). 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 disruptive. Experimental studies have shown that this missense change affects CDKN1B function (PMID: 20824794). 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. |
| OMIM | RCV000162207 | SCV000212164 | pathogenic | Multiple endocrine neoplasia type 4 | 2010-11-01 | no assertion criteria provided | literature only |