Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV003232195 | SCV001224182 | uncertain significance | Sotos syndrome | 2021-08-31 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine with alanine at codon 2382 of the NSD1 protein (p.Thr2382Ala). The threonine residue is weakly conserved and there is a small physicochemical difference between threonine and alanine. This variant is present in population databases (rs765876148, ExAC 0.01%). This variant has not been reported in the literature in individuals affected with NSD1-related conditions. 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 alanine 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. |
Gene |
RCV001546301 | SCV001765797 | likely benign | not provided | 2020-08-07 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Genome- |
RCV003232195 | SCV002055039 | uncertain significance | Sotos syndrome | 2021-07-15 | criteria provided, single submitter | clinical testing |