Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000287363 | SCV000365135 | uncertain significance | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
| Labcorp Genetics |
RCV000287363 | SCV000638705 | uncertain significance | Generalized epilepsy-paroxysmal dyskinesia syndrome | 2024-12-16 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 61 of the KCNMA1 protein (p.Val61Ala). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. 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: 300971). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 |
RCV001557104 | SCV001778804 | uncertain significance | not provided | 2024-12-02 | criteria provided, single submitter | clinical testing | In silico analysis indicates that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
| Fulgent Genetics, |
RCV002494945 | SCV002778092 | uncertain significance | Generalized epilepsy-paroxysmal dyskinesia syndrome; Cerebellar atrophy, developmental delay, and seizures; Epilepsy, idiopathic generalized, susceptibility to, 16; Liang-Wang syndrome | 2022-01-12 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002520631 | SCV003683489 | uncertain significance | Inborn genetic diseases | 2021-10-26 | criteria provided, single submitter | clinical testing | The c.182T>C (p.V61A) alteration is located in exon 1 (coding exon 1) of the KCNMA1 gene. This alteration results from a T to C substitution at nucleotide position 182, causing the valine (V) at amino acid position 61 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |