Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000189133 | SCV000242765 | uncertain significance | not provided | 2017-03-02 | criteria provided, single submitter | clinical testing | The V1087M variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V1087M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution alters a position where amino acids with similar properties to Valine are tolerated across species, and is predicted to be in the cytoplasmic loop between the second and third homologous domains. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
| Invitae | RCV000640626 | SCV000762220 | uncertain significance | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1087 of the SCN2A protein (p.Val1087Met). This variant is present in population databases (rs765278777, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with SCN2A-related conditions. ClinVar contains an entry for this variant (Variation ID: 206984). 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 SCN2A protein function with a negative predictive value of 95%. 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. |
| Mayo Clinic Laboratories, |
RCV000189133 | SCV002541881 | uncertain significance | not provided | 2021-11-26 | criteria provided, single submitter | clinical testing | |
| Revvity Omics, |
RCV000189133 | SCV003820760 | uncertain significance | not provided | 2021-02-18 | criteria provided, single submitter | clinical testing |