Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001069344 | SCV001234506 | uncertain significance | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2023-12-30 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 436 of the KCNMA1 protein (p.Val436Ile). This variant is present in population databases (rs762346849, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNMA1-related conditions. ClinVar contains an entry for this variant (Variation ID: 862595). 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 KCNMA1 protein function with a negative predictive value of 80%. 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 |
RCV002291716 | SCV002584369 | uncertain significance | not provided | 2022-04-15 | criteria provided, single submitter | clinical testing | Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Ambry Genetics | RCV002554575 | SCV003589095 | uncertain significance | Inborn genetic diseases | 2021-11-29 | criteria provided, single submitter | clinical testing | The c.1306G>A (p.V436I) alteration is located in exon 10 (coding exon 10) of the KCNMA1 gene. This alteration results from a G to A substitution at nucleotide position 1306, causing the valine (V) at amino acid position 436 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Ce |
RCV002291716 | SCV004698827 | uncertain significance | not provided | 2024-01-01 | criteria provided, single submitter | clinical testing | KCNMA1: PM2, PP2, PP3 |