Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001226182 | SCV001398484 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2022-03-17 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 283 of the NBN protein (p.Pro283Ser). 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 output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 953831). This missense change has been observed in individual(s) with breast cancer (PMID: 30287823). This variant is not present in population databases (gnomAD no frequency). |
Ambry Genetics | RCV002447134 | SCV002680641 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-01 | criteria provided, single submitter | clinical testing | The p.P283S variant (also known as c.847C>T), located in coding exon 7 of the NBN gene, results from a C to T substitution at nucleotide position 847. The proline at codon 283 is replaced by serine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and serine 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. |
Natera, |
RCV001226182 | SCV002078623 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-07-23 | no assertion criteria provided | clinical testing |