Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000569440 | SCV000662718 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-04-07 | criteria provided, single submitter | clinical testing | The p.K613E variant (also known as c.1837A>G), located in coding exon 11 of the NBN gene, results from an A to G substitution at nucleotide position 1837. The lysine at codon 613 is replaced by glutamic acid, an amino acid with similar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6502 samples (13004 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 175000 alleles tested) in our clinical cohort. This amino acid position is not 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. |
Labcorp Genetics |
RCV001040493 | SCV001204069 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2024-08-11 | criteria provided, single submitter | clinical testing | This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 613 of the NBN protein (p.Lys613Glu). This variant is not present in population databases (gnomAD no frequency). 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: 480042). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamic acid amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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- |
RCV001040493 | SCV002044539 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Baylor Genetics | RCV004569119 | SCV005056192 | uncertain significance | Aplastic anemia | 2023-12-14 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001040493 | SCV002078535 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-02-20 | no assertion criteria provided | clinical testing |