ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1684G>A (p.Val562Ile) (rs754651655)

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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 RCV000575315 SCV000666514 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-06 criteria provided, single submitter clinical testing The p.V562I variant (also known as c.1684G>A), located in coding exon 11 of the NBN gene, results from a G to A substitution at nucleotide position 1684. The valine at codon 562 is replaced by isoleucine, an amino acid with highly similar properties. This amino acid position is somewhat well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics,PreventionGenetics RCV000679453 SCV000806415 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing
Invitae RCV000690804 SCV000818531 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2020-02-12 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 562 of the NBN protein (p.Val562Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs754651655, ExAC 0.01%). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 481829). 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 isoleucine 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.
Color Health, Inc RCV000575315 SCV000910918 likely benign Hereditary cancer-predisposing syndrome 2016-11-17 criteria provided, single submitter clinical testing

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