ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.509C>T (p.Pro170Leu)

gnomAD frequency: 0.00003  dbSNP: rs587782411
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131450 SCV000186434 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-19 criteria provided, single submitter clinical testing The p.P170L variant (also known as c.509C>T) is located in coding exon 5 of the NBN gene. This alteration results from a C to T substitution at nucleotide position 509. The proline at codon 170 is replaced by leucine, an amino acid with similar properties. In one study, this alteration was observed in 1/3236 cases with invasive epithelial ovarian cancer and 0/3431 controls (Ramus SJ et al. J. Natl. Cancer Inst. 2015 Nov;107(11). Based on protein sequence alignment, 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 RCV000457816 SCV000553070 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2023-11-01 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 170 of the NBN protein (p.Pro170Leu). This variant is present in population databases (rs587782411, gnomAD 0.002%). This missense change has been observed in individual(s) with serous ovarian cancer (PMID: 26315354). ClinVar contains an entry for this variant (Variation ID: 142367). 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.
Genome-Nilou Lab RCV000457816 SCV002045192 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Baylor Genetics RCV003474777 SCV004199696 uncertain significance Aplastic anemia 2023-01-25 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000131450 SCV000886694 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-24 no assertion criteria provided clinical testing

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