Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV001013789 | SCV001174418 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-24 | criteria provided, single submitter | clinical testing | The p.Q65R variant (also known as c.194A>G), located in coding exon 1 of the CDKN1B gene, results from an A to G substitution at nucleotide position 194. The glutamine at codon 65 is replaced by arginine, an amino acid with highly similar properties. 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. |
Invitae | RCV001243763 | SCV001416944 | uncertain significance | Multiple endocrine neoplasia type 4 | 2020-09-16 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals with CDKN1B-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glutamine with arginine at codon 65 of the CDKN1B protein (p.Gln65Arg). The glutamine residue is highly conserved and there is a small physicochemical difference between glutamine and arginine. |
Baylor Genetics | RCV001243763 | SCV004212408 | uncertain significance | Multiple endocrine neoplasia type 4 | 2023-07-07 | criteria provided, single submitter | clinical testing |