Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000188216 | SCV000241823 | uncertain significance | not provided | 2020-06-29 | criteria provided, single submitter | clinical testing | Reported in a patient with a neurodevelopmental disorder (Lindy et al., 2018); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29655203) |
Invitae | RCV000707280 | SCV000836370 | uncertain significance | Lafora disease | 2022-07-26 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 381 of the NHLRC1 protein (p.Asp381Gly). This variant is present in population databases (rs200201752, gnomAD 0.004%). This missense change has been observed in individual(s) with NHLRC1-related conditions (PMID: 29655203). ClinVar contains an entry for this variant (Variation ID: 206192). 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 NHLRC1 protein function. 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. |