Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001220252 | SCV001392232 | uncertain significance | Multiple endocrine neoplasia type 4 | 2022-09-14 | criteria provided, single submitter | clinical testing | 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. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 948905). This missense change has been observed in individual(s) with pituitary adenoma and somatotropinoma (PMID: 22291433). This variant is present in population databases (rs758686055, gnomAD 0.003%). This sequence change replaces serine, which is neutral and polar, with threonine, which is neutral and polar, at codon 56 of the CDKN1B protein (p.Ser56Thr). |
Ambry Genetics | RCV002402662 | SCV002712827 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-08-26 | criteria provided, single submitter | clinical testing | The p.S56T variant (also known as c.167G>C), located in coding exon 1 of the CDKN1B gene, results from a G to C substitution at nucleotide position 167. The serine at codon 56 is replaced by threonine, an amino acid with similar properties. In one study, this alteration was reported in two brothers from a familial isolated pituitary adenoma family with a somatotropinoma and pituitary adenoma, and was also reported in unaffected controls (Tichomirowa MA et al. Endocr Relat Cancer, 2012 Jun;19:233-41). This amino acid position is not well conserved in available 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. |
Gene |
RCV003238846 | SCV003936348 | uncertain significance | not provided | 2022-12-30 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Identified in two brothers with pituitary adenomas, but also identified in control individuals (Tichomirowa et al., 2012); This variant is associated with the following publications: (PMID: 22291433, 23800691) |