ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.935T>C (p.Leu312Ser)

gnomAD frequency: 0.00003  dbSNP: rs371480039
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000132302 SCV000187387 uncertain significance Hereditary cancer-predisposing syndrome 2023-02-15 criteria provided, single submitter clinical testing The p.L312S variant (also known as c.935T>C), located in coding exon 8 of the NBN gene, results from a T to C substitution at nucleotide position 935. The leucine at codon 312 is replaced by serine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000528665 SCV000634343 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2023-10-16 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 312 of the NBN protein (p.Leu312Ser). This variant is present in population databases (rs371480039, gnomAD 0.02%). 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: 142859). 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.
GeneDx RCV001557142 SCV001778849 uncertain significance not provided 2023-08-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24894818)
Genome-Nilou Lab RCV000528665 SCV002044749 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Sema4, Sema4 RCV000132302 SCV002536726 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-17 criteria provided, single submitter curation
Baylor Genetics RCV003474787 SCV004199656 uncertain significance Aplastic anemia 2024-02-29 criteria provided, single submitter clinical testing
Natera, Inc. RCV000528665 SCV002078613 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-03-21 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.