Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000437020 | SCV000535188 | uncertain significance | not provided | 2018-11-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CHRNA2 gene. The P290L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P290L variant is observed on 11/33582 (0.03%) alleles from individuals of Latino background in large population cohorts, which is greater than expected for this disorder (Lek et al., 2016). The P290L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This amino acid substitution is not predicted to occur within the transmembrane region of the protein, where the vast majority of pathogenic missense variants have been identified in association with epilepsy (Steinlein et al., 2010). However, in silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Invitae | RCV001038713 | SCV001202199 | likely benign | Autosomal dominant nocturnal frontal lobe epilepsy | 2022-11-24 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV002488973 | SCV002775630 | uncertain significance | Autosomal dominant nocturnal frontal lobe epilepsy 4 | 2021-09-10 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002522663 | SCV003682118 | likely benign | Inborn genetic diseases | 2021-07-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |