Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000171062 | SCV000223626 | uncertain significance | not provided | 2023-01-26 | criteria provided, single submitter | clinical testing | Reported using an alternate transcript of the gene; Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation as the last 90 amino acids are lost, although loss-of-function variants have not been reported downstream of this position in the protein; This variant is associated with the following publications: (PMID: 34426522, 31737628, 29758173, 28449774, 22247482, 18464934) |
Invitae | RCV000009836 | SCV000959398 | likely pathogenic | Brugada syndrome 5 | 2023-09-17 | 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. This variant disrupts a region of the SCN1B protein in which other variant(s) (p.Pro184Leu) have been observed in individuals with SCN1B-related conditions (Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. Experimental studies have shown that this premature translational stop signal affects SCN1B function (PMID: 18464934). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 9254). This premature translational stop signal has been observed in individual(s) with Brugada syndrome, sudden arrythmic death syndrome and progressive familial heart block type 1 (PMID: 18464934, 22247482, 28449774, 29758173). This variant is present in population databases (rs267607028, gnomAD 0.002%). This sequence change creates a premature translational stop signal (p.Trp179*) in the SCN1B gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 90 amino acid(s) of the SCN1B protein. |
OMIM | RCV000009836 | SCV000030057 | pathogenic | Brugada syndrome 5 | 2008-06-01 | no assertion criteria provided | literature only |