Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000646742 | SCV000768527 | uncertain significance | Brugada syndrome 5 | 2022-09-27 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 139 of the SCN1B protein (p.Val139Ile). This variant is present in population databases (rs560827790, gnomAD 0.006%). This variant has not been reported in the literature in individuals affected with SCN1B-related conditions. ClinVar contains an entry for this variant (Variation ID: 537730). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 |
RCV001766391 | SCV001991642 | uncertain significance | not provided | 2019-07-29 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Reported in ClinVar as a variant of uncertain significance (ClinVar Variant ID# 537730; Landrum et al., 2016); Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function |
Ce |
RCV001766391 | SCV002063755 | uncertain significance | not provided | 2021-12-01 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002331207 | SCV002630398 | likely benign | Cardiovascular phenotype | 2020-03-25 | 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. |
Fulgent Genetics, |
RCV002507107 | SCV002814181 | uncertain significance | Generalized epilepsy with febrile seizures plus, type 1; Brugada syndrome 5; Atrial fibrillation, familial, 13; Developmental and epileptic encephalopathy, 52 | 2022-01-07 | criteria provided, single submitter | clinical testing |