ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.335C>T (p.Pro112Leu)

gnomAD frequency: 0.00003  dbSNP: rs759723870
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001020084 SCV001181515 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-29 criteria provided, single submitter clinical testing The p.P112L variant (also known as c.335C>T), located in coding exon 4 of the NBN gene, results from a C to T substitution at nucleotide position 335. The proline at codon 112 is replaced by leucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Invitae RCV001233028 SCV001405605 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2022-10-05 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 112 of the NBN protein (p.Pro112Leu). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 823660). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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 RCV001233028 SCV002045230 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing
Natera, Inc. RCV001233028 SCV002078669 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-06-16 no assertion criteria provided clinical testing

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