Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV002233283 | SCV000823614 | uncertain significance | Autosomal dominant epilepsy with auditory features | 2023-02-02 | criteria provided, single submitter | clinical testing | 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. 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 not expected to disrupt LGI1 protein function. ClinVar contains an entry for this variant (Variation ID: 573459). This variant has not been reported in the literature in individuals affected with LGI1-related conditions. This variant is present in population databases (rs370151711, gnomAD 0.007%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 209 of the LGI1 protein (p.Arg209His). |
| Ambry Genetics | RCV002360765 | SCV002660024 | uncertain significance | Inborn genetic diseases | 2018-01-11 | criteria provided, single submitter | clinical testing | The p.R209H variant (also known as c.626G>A), located in coding exon 6 of the LGI1 gene, results from a G to A substitution at nucleotide position 626. The arginine at codon 209 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is highly conserved through mammals but not in all available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |