Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV002322930 | SCV002610813 | uncertain significance | Inborn genetic diseases | 2021-09-20 | criteria provided, single submitter | clinical testing | The p.E1067K variant (also known as c.3199G>A), located in coding exon 21 of the NPC1 gene, results from a G to A substitution at nucleotide position 3199. The glutamic acid at codon 1067 is replaced by lysine, an amino acid with similar properties. This amino acid position is conserved. 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 |
RCV003099283 | SCV003266965 | uncertain significance | Niemann-Pick disease, type C1 | 2022-09-07 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1067 of the NPC1 protein (p.Glu1067Lys). This variant is present in population databases (rs779353327, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with NPC1-related conditions. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt NPC1 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. |