Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001893919 | SCV002170734 | uncertain significance | Niemann-Pick disease, type C1 | 2022-03-02 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 91 of the NPC1 protein (p.Leu91Val). This variant is not present in population databases (gnomAD no frequency). 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. |
| Ambry Genetics | RCV002425204 | SCV002744325 | uncertain significance | Inborn genetic diseases | 2022-03-25 | criteria provided, single submitter | clinical testing | The p.L91V variant (also known as c.271C>G), located in coding exon 3 of the NPC1 gene, results from a C to G substitution at nucleotide position 271. The leucine at codon 91 is replaced by valine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |