Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001223249 | SCV001395388 | likely pathogenic | Leber congenital amaurosis 9 | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 178 of the NMNAT1 protein (p.Val178Met). This variant is present in population databases (rs757724544, gnomAD 0.01%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 22842229; internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 951357). Invitae Evidence 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 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 NMNAT1 protein function. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Laboratory of Genetics in Ophthalmology, |
RCV001223249 | SCV001433026 | likely pathogenic | Leber congenital amaurosis 9 | no assertion criteria provided | research |