Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001317636 | SCV001508305 | uncertain significance | Familial hemiplegic migraine | 2023-03-29 | 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. This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 686 of the ATP1A2 protein (p.Val686Ile). This variant is present in population databases (rs780606939, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of autosomal dominant ATP1A2-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 1018352). 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 ATP1A2 protein function. This variant disrupts the p.Val686 amino acid residue in ATP1A2. Other variant(s) that disrupt this residue have been observed in individuals with ATP1A2-related conditions (PMID: 34992632; Invitae), which suggests that this may be a clinically significant amino acid residue. |
Revvity Omics, |
RCV003145562 | SCV003832801 | uncertain significance | not provided | 2020-07-17 | criteria provided, single submitter | clinical testing |