ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1034G>T (p.Gly345Val) (rs587780089)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000212740 SCV000149683 uncertain significance not provided 2017-10-25 criteria provided, single submitter clinical testing This variant is denoted NBN c.1034G>T at the cDNA level, p.Gly345Val (G345V) at the protein level, and results in the change of a Glycine to a Valine (GGC>GTC). This variant has been observed in at least one individual with endometrial cancer (Ring 2016). NBN Gly345Val was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Glycine and Valine share similar properties, this is considered a conservative amino acid substitution. NBN Gly345Val occurs at a position that is not conserved and is not in a known functional domain. In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available information, it is unclear whether NBN Gly345Val is pathogenic or benign. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000115774 SCV000183871 uncertain significance Hereditary cancer-predisposing syndrome 2018-09-23 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000476299 SCV000553124 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces glycine with valine at codon 345 of the NBN protein (p.Gly345Val). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and valine. This variant is present in population databases (rs587780089, ExAC 0.009%). This variant has been reported in an individual affected with endometrial cancer (PMID: 27443514). ClinVar contains an entry for this variant (Variation ID: 127852). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000764783 SCV000895927 uncertain significance Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2018-10-31 criteria provided, single submitter clinical testing
Color RCV000115774 SCV000903211 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-23 criteria provided, single submitter clinical testing

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