Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000709064 | SCV000838322 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2018-07-02 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000709064 | SCV001537459 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2022-12-31 | 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 are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 584730). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 33 of the NBN protein (p.Ile33Val). |
Genome- |
RCV000709064 | SCV002045287 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001188198 | SCV004008198 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-11 | criteria provided, single submitter | clinical testing | The p.I33V variant (also known as c.97A>G), located in coding exon 2 of the NBN gene, results from an A to G substitution at nucleotide position 97. The isoleucine at codon 33 is replaced by valine, an amino acid with highly similar properties. This alteration was detected in a cohort of 1663 Brazilian breast cancer patients who underwent hereditary multigene panel testing (Guindalini RSC et al. Sci Rep, 2022 Mar;12:4190). This amino acid position is highly 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. |
Natera, |
RCV000709064 | SCV002078694 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2020-11-17 | no assertion criteria provided | clinical testing |