Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001256667 | SCV003522718 | uncertain significance | Leber congenital amaurosis 9 | 2022-01-16 | criteria provided, single submitter | clinical testing | This variant is present in population databases (no rsID available, gnomAD 0.0009%). This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 251 of the NMNAT1 protein (p.His251Pro). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 22842229). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. 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"). ClinVar contains an entry for this variant (Variation ID: 978262). |
Laboratory of Genetics in Ophthalmology, |
RCV001256667 | SCV001433044 | likely pathogenic | Leber congenital amaurosis 9 | no assertion criteria provided | research |