ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.340G>T (p.Val114Phe) (rs771034958)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000220601 SCV000273508 uncertain significance Hereditary cancer-predisposing syndrome 2017-06-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (deleterious) and/or completely conserved position in appropriate species
Color RCV000220601 SCV000685774 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-02 criteria provided, single submitter clinical testing
Counsyl RCV000206877 SCV000794974 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2017-10-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764790 SCV000895934 uncertain significance Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV000767209 SCV000566663 uncertain significance not provided 2016-10-18 criteria provided, single submitter clinical testing This variant is denoted NBN c.340G>T at the cDNA level, p.Val114Phe (V114F) at the protein level, and results in the change of a Valine to a Phenylalanine (GTT>TTT). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Val114Phe was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Valine and Phenylalanine differ in some properties, this is considered a semi-conservative amino acid substitution. NBN Val114Phe occurs at a position that is conserved across species and is located in the BRCT domain and the region that mediates interaction with SP100 (UniProt). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether NBN Val114Phe is pathogenic or benign. We consider it to be a variant of uncertain significance.
Invitae RCV000206877 SCV000259635 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-11-02 criteria provided, single submitter clinical testing This sequence change replaces valine with phenylalanine at codon 114 of the NBN protein (p.Val114Phe). The valine residue is highly conserved and there is a small physicochemical difference between valine and phenylalanine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in an individual with personal and family history of breast cancer, uterine cancer and ovarian cancer (PMID: 28202063). ClinVar contains an entry for this variant (Variation ID: 219644). 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: "Deleterious"; PolyPhen-2: "Probably 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000486552 SCV000601689 uncertain significance not specified 2017-07-21 criteria provided, single submitter clinical testing

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