Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000589483 | SCV000699973 | uncertain significance | not provided | 2016-04-04 | criteria provided, single submitter | clinical testing | Variant Summary: The variant of interest causes a missense change involving a conserved nucleotide with 2/4 in silico programs predicting a "benign" outcome and 2/4 predicting a "deleterious" outcome, although these predictions have yet to be functionally assessed. The variant of interest was not observed in controls (ExAC, 1000 Gs or ESP), nor has it been, to our knowledge, reported in affected individuals via publications and/or reputable clinical laboratories/databases. Therefore, taking all available lines of evidence into consideration, the variant of interest is classified as a "Variant of Uncertain Significance (VUS)," until additional information becomes available. |
| Labcorp Genetics |
RCV002530944 | SCV003516847 | uncertain significance | Long QT syndrome 10 | 2022-03-08 | criteria provided, single submitter | clinical testing | 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. 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. ClinVar contains an entry for this variant (Variation ID: 496553). This variant has not been reported in the literature in individuals affected with SCN4B-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 197 of the SCN4B protein (p.Lys197Glu). |