Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000166078 | SCV000216841 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-08-16 | criteria provided, single submitter | clinical testing | The c.1008_1010dupAAC variant (also known as p.T337dup), located in coding exon 9 of the NBN gene, results from an in-frame duplication of AAC at nucleotide positions 1008 to 1010. This results in the duplication of an extra threonine residue between codons 337 and 338. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Labcorp Genetics |
RCV000465315 | SCV000553114 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2024-12-24 | criteria provided, single submitter | clinical testing | This variant, c.1008_1010dup, results in the insertion of 1 amino acid(s) of the NBN protein (p.Thr337dup), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 186477). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. |
| Gene |
RCV000483396 | SCV000571923 | uncertain significance | not provided | 2022-12-29 | criteria provided, single submitter | clinical testing | In-frame insertion of 1 amino acid in a non-repeat region; In silico analysis supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000483396 | SCV004222107 | uncertain significance | not provided | 2022-10-17 | criteria provided, single submitter | clinical testing | The variant has not been reported in the published literature. The frequency of this variant in the general population, 0.0000066 (1/152190 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. Based on the available information, we are unable to determine the clinical significance of this variant. |