Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000733303 | SCV000861351 | uncertain significance | not provided | 2018-05-18 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV001335214 | SCV001528307 | uncertain significance | Niemann-Pick disease, type C1 | 2018-03-14 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. The c.2848G>A (p.V950M) variant has been previously reported in multiple patients with adult-onset Niemann-Pick disease and variant biochemical phenotype [PMID 11333381, 16126423, 26984608, 27900365] |
| Invitae | RCV001335214 | SCV003269553 | uncertain significance | Niemann-Pick disease, type C1 | 2023-10-22 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 981 of the NPC1 protein (p.Pro981Leu). 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. ClinVar contains an entry for this variant (Variation ID: 597245). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on 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. |