ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.2071G>A (p.Val691Ile)

gnomAD frequency: 0.00001  dbSNP: rs772059959
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000227442 SCV000287463 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2024-10-24 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 691 of the NBN protein (p.Val691Ile). This variant is present in population databases (rs772059959, gnomAD 0.002%). 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: 239192). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
Ambry Genetics RCV000575268 SCV000670198 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-30 criteria provided, single submitter clinical testing The p.V691I variant (also known as c.2071G>A) is located in coding exon 14 of the NBN gene. The valine at codon 691 is replaced by isoleucine, an amino acid with highly similar properties. This change occurs in the first base pair of coding exon 14. This amino acid position is 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.
Genome-Nilou Lab RCV000227442 SCV002046069 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV004567725 SCV005056217 uncertain significance Aplastic anemia 2023-11-06 criteria provided, single submitter clinical testing

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