Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000030767 | SCV003522738 | uncertain significance | Leber congenital amaurosis 9 | 2022-04-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 151 of the NMNAT1 protein (p.Val151Phe). This variant is present in population databases (rs387907292, gnomAD 0.0009%). This missense change has been observed in individual(s) with Leber congenital amaurosis (PMID: 22842230, 22842231). ClinVar contains an entry for this variant (Variation ID: 37136). 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"). Experimental studies have shown that this missense change affects NMNAT1 function (PMID: 22842230, 26018082). 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. |
| OMIM | RCV000030767 | SCV000053428 | pathogenic | Leber congenital amaurosis 9 | 2012-09-01 | no assertion criteria provided | literature only |