Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001056282 | SCV001220717 | uncertain significance | Niemann-Pick disease, type C1 | 2020-01-20 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine with methionine at codon 1061 of the NPC1 protein (p.Ile1061Met). The isoleucine residue is highly conserved and there is a small physicochemical difference between isoleucine and methionine. 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. This variant disrupts the p.Ile1061 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 10521297, 16126423, 25149939, 20521171). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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 C0"). This variant has been observed in an individual with clinical features of Niemann-Pick type C (Invitae). This variant is not present in population databases (ExAC no frequency). |