Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000463765 | SCV000551867 | uncertain significance | Lafora disease | 2019-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine with cysteine at codon 140 of the NHLRC1 protein (p.Arg140Cys). The arginine residue is highly conserved and there is a large physicochemical difference between arginine and cysteine. This variant is present in population databases (rs148035405, ExAC 0.008%). This variant has not been reported in the literature in individuals with NHLRC1-related disease. ClinVar contains an entry for this variant (Variation ID: 410971). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. |
Gene |
RCV002281096 | SCV002569661 | uncertain significance | not provided | 2022-02-28 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |