Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001227877 | SCV001400255 | pathogenic | Microcephaly, normal intelligence and immunodeficiency | 2021-10-18 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln506*) in the NBN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040). 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. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 955271). |
| Ambry Genetics | RCV003294092 | SCV003999797 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-06-04 | criteria provided, single submitter | clinical testing | The p.Q506* pathogenic mutation (also known as c.1516C>T), located in coding exon 11 of the NBN gene, results from a C to T substitution at nucleotide position 1516. This changes the amino acid from a glutamine to a stop codon within coding exon 11. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |