Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Center for Human Genetics, |
RCV000660196 | SCV000782194 | uncertain significance | Sotos syndrome 1 | 2016-11-01 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000685447 | SCV000812929 | uncertain significance | Beckwith-Wiedemann syndrome | 2018-01-12 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid with histidine at codon 2511 of the NSD1 protein (p.Asp2511His). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and histidine. This variant is present in population databases (rs575229932, ExAC 0.009%). This variant has not been reported in the literature in individuals with NSD1-related disease. 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: "Tolerated"; PolyPhen-2: "Possibly 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. |