ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.119C>T (p.Ser40Leu) (rs587781530)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000129524 SCV000184300 uncertain significance Hereditary cancer-predisposing syndrome 2019-11-04 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV000232275 SCV000287447 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2019-07-25 criteria provided, single submitter clinical testing This sequence change replaces serine with leucine at codon 40 of the NBN protein (p.Ser40Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs587781530, ExAC 0.003%). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 141146). Algorithms developed to predict the effect of missense changes on protein structure and function 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.
GeneDx RCV000586924 SCV000572565 uncertain significance not provided 2017-08-23 criteria provided, single submitter clinical testing This variant is denoted NBN c.119C>T at the cDNA level, p.Ser40Leu (S40L) at the protein level, and results in the change of a Serine to a Leucine (TCG>TTG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. NBN Ser40Leu was not observed at a significant allele frequency in large population cohorts (Lek 2016). Since Serine and Leucine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. NBN Ser40Leu occurs at a position that is conserved across species and is located in the FHA domain (Damiola 2014). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available evidence, it is unclear whether NBN Ser40Leu is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000129524 SCV000685700 uncertain significance Hereditary cancer-predisposing syndrome 2019-08-26 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000586924 SCV000697939 uncertain significance not provided 2016-01-25 criteria provided, single submitter clinical testing
Counsyl RCV000232275 SCV000789033 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2016-12-27 criteria provided, single submitter clinical testing
GeneKor MSA RCV000129524 SCV000822083 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-01 criteria provided, single submitter clinical testing
Mendelics RCV000232275 SCV000838321 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000764791 SCV000895935 uncertain significance Microcephaly, normal intelligence and immunodeficiency; Aplastic anemia; Acute lymphoid leukemia 2018-10-31 criteria provided, single submitter clinical testing

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