Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000810034 | SCV000950220 | uncertain significance | Brugada syndrome 5 | 2018-10-30 | criteria provided, single submitter | clinical testing | This sequence change replaces cysteine with tyrosine at codon 181 of the SCN1B protein (p.Cys181Tyr). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and tyrosine. The SCN1B gene has multiple clinically relevant transcripts. The p.Cys181Tyr variant occurs in alternate transcript NM_001037.4, which corresponds to position c.*5112G>A in NM_199037.3, the primary transcript listed in the Methods. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with SCN1B-related disease. 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: "Not Available"; Align-GVGD: "Class C0"). 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. |