Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center For Human Genetics And Laboratory Diagnostics, |
RCV000623989 | SCV000740279 | likely pathogenic | Developmental and epileptic encephalopathy, 7 | 2017-11-09 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000624475 | SCV000742132 | likely pathogenic | Inborn genetic diseases | 2017-01-12 | criteria provided, single submitter | clinical testing | |
| Illumina Laboratory Services, |
RCV001249752 | SCV001423785 | likely pathogenic | KCNQ2-Related Disorders | 2019-12-06 | criteria provided, single submitter | clinical testing | The KCNQ2 c.430C>G (p.Arg144Gly) variant is a missense variant that has been reported in a heterozygous state in one affected individual with a Rett-like phenotype (Vidal et al. 2019). The affected individual is specifically noted to have psychomotor delay and intellectual disability, but no developmental regression or breathing problems; no additional phenotypes were described. The p.Arg144Gly variant is not found in the Genome Aggregation Database despite good sequence coverage, so the variant is presumed to be rare. Two additional variants at the Arg144 residue have been described in literature, including p.Arg144Gln in an infant who presented with infantile spasms without seizures, global developmental delays, poor eye contact, no speech, inability to walk, and bilateral enlarged kidneys were also noted (Epi4K Consortium et al. 2013). The second variant at the Arg144 residue was identified in an affected individual with intellectual disability, but no additional phenotypes were described (Lelieveld et al. 2016). The p.Arg144Gly variant is located in the third segment of the transmembrane domain (Vidal et al. 2019). Based on the de novo state, absence from population frequency databases, and additional clinical evidence for the Arg144 residue, the p.Arg144Gly variant is classified as likely pathogenic for KCNQ2-related disorders. |
| Rady Children's Institute for Genomic Medicine, |
RCV001249752 | SCV004046117 | pathogenic | KCNQ2-Related Disorders | criteria provided, single submitter | clinical testing | This variant has been previously reported as heterozygous, unknown inheritance, in a patient with Rett-like syndrome (PMID: 31105003). Two other missense changes affecting the same amino acid residue have been reported as de novo changes in patients with neurodevelopmental disorders (c.430C>T (p.Arg144Trp); PMID: 28628100) and seizure disorders including epileptic encephalopathy and infantile spasms (c.431G>A (p.Arg144Gln); PMID: 23934111, 29186148, 30174244). It is absent from the gnomAD population database and thus is presumed to be rare. The c.430C>G (p.Arg144Gly) variant affects a highly conserved amino acid and is predicted by multiple in silico tools to have a deleterious effect on protein function. Analysis of the parental samples was negative for the variant, indicating this variant likely occurred as a de novo event. Based on the available evidence, the c.430C>G (p.Arg144Gly) variant is classified as Pathogenic. |