Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000189174 | SCV000242806 | pathogenic | not provided | 2019-04-11 | criteria provided, single submitter | clinical testing | Identified in a patient with epilepsy and inherited from a mildly affected mother, who was mosaic for the variant, in published literature (Stosser et al., 2018).; Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; The majority of missense variants in this gene are considered pathogenic (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 28837158, 33278787) |
Invitae | RCV001852500 | SCV002286048 | likely pathogenic | Seizures, benign familial infantile, 3; Developmental and epileptic encephalopathy, 11 | 2022-03-18 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 207022). This missense change has been observed in individual(s) with clinical features of SCN2A-related disease (PMID: 28837158, 33278787; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 1636 of the SCN2A protein (p.Ile1636Met). |