Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001326911 | SCV001517965 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-07-03 | criteria provided, single submitter | clinical testing | 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. 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: "Possibly Damaging"; Align-GVGD: "Class C15"). This variant has not been reported in the literature in individuals with NBN-related conditions. This variant is present in population databases (rs762376159, ExAC 0.001%). This sequence change replaces serine with cysteine at codon 355 of the NBN protein (p.Ser355Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. |
Genome- |
RCV001326911 | SCV002044715 | uncertain significance | Microcephaly, normal intelligence and immunodeficiency | 2021-11-07 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV001188076 | SCV002716303 | uncertain significance | Hereditary cancer-predisposing syndrome | 2020-02-13 | criteria provided, single submitter | clinical testing | The p.S355C variant (also known as c.1063A>T), located in coding exon 9 of the NBN gene, results from an A to T substitution at nucleotide position 1063. The serine at codon 355 is replaced by cysteine, an amino acid with dissimilar properties. 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. |