Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001322683 | SCV001513567 | uncertain significance | Atrial fibrillation, familial, 14 | 2021-05-03 | 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 sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SCN2B-related conditions. This variant is present in population databases (rs142643516, ExAC 0.001%). This sequence change replaces methionine with isoleucine at codon 79 of the SCN2B protein (p.Met79Ile). The methionine residue is highly conserved and there is a small physicochemical difference between methionine and isoleucine. |
| Ambry Genetics | RCV002456443 | SCV002737031 | uncertain significance | Cardiovascular phenotype | 2021-10-22 | criteria provided, single submitter | clinical testing | The p.M79I variant (also known as c.237G>C), located in coding exon 2 of the SCN2B gene, results from a G to C substitution at nucleotide position 237. The methionine at codon 79 is replaced by isoleucine, an amino acid with highly similar properties. However, this change occurs in the last base pair of coding exon 2 and may have some effect on normal mRNA splicing. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. This amino acid position is not well conserved in available vertebrate species. In addition, as a missense substitution this is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |
| Fulgent Genetics, |
RCV001322683 | SCV002781521 | uncertain significance | Atrial fibrillation, familial, 14 | 2021-10-01 | criteria provided, single submitter | clinical testing |