Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Blueprint Genetics | RCV001074108 | SCV001239677 | pathogenic | Retinal dystrophy | 2019-01-05 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV001551709 | SCV001772275 | likely pathogenic | not provided | 2021-07-08 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate that this variant leads to reduced protein stability and enzymatic activity (Sasaki et al., 2015); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 32865313, 27535533, 22842227, 22842230, 26018082, 22842231) |
| Invitae | RCV001256659 | SCV002119164 | pathogenic | Leber congenital amaurosis 9 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 98 of the NMNAT1 protein (p.Val98Gly). This variant is present in population databases (rs771336246, gnomAD 0.02%). This missense change has been observed in individual(s) with clinical features of NMNAT1-related conditions (PMID: 22842227, 22842231; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 866255). 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 expected to disrupt NMNAT1 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects NMNAT1 function (PMID: 26018082). For these reasons, this variant has been classified as Pathogenic. |
| Greenwood Genetic Center Diagnostic Laboratories, |
RCV002221606 | SCV002499105 | likely pathogenic | Spondyloepiphyseal dysplasia, sensorineural hearing loss, impaired intellectual development, and leber congenital amaurosis | 2022-03-09 | criteria provided, single submitter | clinical testing | PS3, PM2, PM3, PP3 |
| Laboratory of Genetics in Ophthalmology, |
RCV001256659 | SCV001433035 | likely pathogenic | Leber congenital amaurosis 9 | no assertion criteria provided | research |