Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000187983 | SCV000241586 | uncertain significance | not provided | 2017-08-24 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the KCNQ3 gene. The c.1599dupA variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1599dupA variant causes a frameshift starting with codon Phenylalanine 534, changes this amino acid to an Isoleucine residue and creates a premature Stop codon at position 15 of the new reading frame, denoted p.Phe534IlefsX15. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Based on the currently available information, it is unclear whether the c.1599dupA variant is a pathogenic variant or a rare benign variant. |
| Labcorp Genetics |
RCV001380941 | SCV001579168 | pathogenic | Benign neonatal seizures | 2022-04-01 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 205978). This premature translational stop signal has been observed in individual(s) with KCNQ3-related conditions (PMID: 31440727). 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 sequence change creates a premature translational stop signal (p.Phe534Ilefs*15) in the KCNQ3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in KCNQ3 are known to be pathogenic (PMID: 29383681, 29852413). For these reasons, this variant has been classified as Pathogenic. |
| Equipe Genetique des Anomalies du Developpement, |
RCV000824971 | SCV000966146 | pathogenic | Seizure; Intellectual disability | 2017-02-22 | no assertion criteria provided | clinical testing |