Table 3.
Summary of SCN10A Rare Variants Associated with Brugada Syndrome.
| Rare Variant | Reported ID | Exon | Type | Change in nucleotide | Change in amino acid | Codons | Location | Global MAF (1000genome) | Global MAF (ESP) | Number of Unrelated individuals | Number of Family members | SIFT-Score | SIFT-Prediction | Polyphen-Score | Polyphen-Prediction | Conservation (phast Cons)* | Conservation (GERP)† |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R14L | rs141207048 | 1 | missense | p.Arg14 Leu | c.41G>T | CGT/CTT | N-terminal | 0.002 | 0.002153 | 5 | 2 | 0 | deleterious | 0.998 | probably damaging | 0.987 | 2.32 |
| T137M | rs148663098 | 3 | missense | p.Thr137 Met | c.410C>T | ACG/ATG | DI-SI | 0 | 0.000077 | 1 | 0 | 1 | tolerated | 0.022 | benign | 0.077 | 3.26 |
| I206M | rs74717885 | 5 | missense | p.Ile206 Met | c.618A>G | ATA/ATG | DI-SIII | 0.048 | 0.01161 | 4 | 0 | 0.01 | deleterious | 0.082 | benign | 0.001 | -0.84 |
| S242T | rs140288103 | 6 | missense | p.Ser242 Thr | c.724T>A | TCA/ACA | DI-S4/S5 | 0 | 0.000231 | 1 | 0 | 0 | deleterious | 0.999 | probably damaging | 0.997 | 4.69 |
| F386C | rs78555408 | 9 | missense | p.Phe386 Cys | c.1157T>G | TTC/TGC | DI-S6 | 0.002 | N/A | 1 | 1 | 0 | deleterious | 1 | probably damaging | 1 | 5.21 |
| L388P | rs199734710 | 9 | missense | p.Leu388 Pro | c.1163T>C | CTG/CCG | DI-S6 | 0.001 | 0.000231 | 1 | 0 | 0 | deleterious | 1 | probably damaging | 1 | 5.21 |
| V620I | rs151303346 | 12 | missense | p.Val620 Ile | c.1858G>A | GTC/ATC | DI/DII | 0 | 0.000384 | 1 | 0 | 0.03 | deleterious | 0.999 | probably damaging | 0.818 | 4.6 |
| F938YFSX12 | N/A | 16 | Frame shift | p.Phe938 Tyr FsX12 | c.2813-2814 delinA | ‡ | DII/DIII | N/A | N/A | 1 | 1 | N/A | N/A | N/A | N/A | N/A | N/A |
| D1080N | TMPESP3 38765035 | 18 | missense | p.Asp1080 Asn | c.3238G>A | GAC/AAC | DII/DIII | 0 | 0.000077 | 1 | 0 | 0.17 | tolerated | 0.967 | probably damaging | 0.75 | 4.82 |
| I1225T | rs139638446 | 20 | missense | p.Ile1225 Thr | c.3674 T>C | ATT/ACT | DIII-S4 | 0 | 0.000461 | 2 | 0 | 0 | deleterious | 1 | probably damaging | 0.992 | 4.45 |
| R1268Q | rs138832868 | 21 | missense/near-splice | p.Arg1268 Gln | c.3803G>A | CGG/CAG | DIII-S4/S5 | 0.001 | 0.002076 | 1 | 1 | 0 | deleterious | 0.741 | probably damaging | 1 | 4.14 |
| S1337T | rs11711062 | 22 | missense | p.Ser1337 Thr | c.4009T>A | TCC/ACC | DIII-S5/S6 | 0.001 | 0.004536 | 1 | 0 | 0.61 | tolerated | 0.059 | benign | 0 | -9.34 |
| G1406D | N/A | 24 | missense | p.Gly1406 Asp | c.4217G>A | GGC/GAC | DIII-S6 | N/A | N/A | 1 | 0 | 0 | deleterious | 0.999 | probably damaging | 1 | 5.11 |
| G1662S | rs151090729 | 27 | missense | p.Gly1662 Ser | c.4984G>A | GGC/AGC | DIV-S5/S6 | 0.001 | 0.001307 | 3 | 2 | 0 | deleterious | 1 | probably damaging | 0.969 | 5.38 |
| V1697I | rs77804526 | 27 | missense | p.Val1697 Ile | c.5089G>A | GTA/ATA | DIV-S5/S6 | 0.004 | 0.010072 | 4 | 0 | 0.3 7 | tolerated | 0.098 | benign | 0.138 | 0.24 |
| N1715T | N/A | 27 | missense | p.Asn1715 Thr | c.5144A>C | AAC/ACC | DIV-S6 | N/A | N/A | 1 | 0 | 0 | deleterious | 1 | probably damaging | 1 | 4.19 |
| R1869C | rs141648641 | 27 | missense | p.Arg1869 Cys | c.5605C>T | CGC/TGC | C-terminal | 0 | 0.000923 | 2 | 0 | 0 | deleterious | 1 | probably damaging | 0.945 | 5.09 |
N/A: not available; 1000 genome: the 1000 Human Genome Project Database; ESP: Exome Sequencing Project; MAF: the Minor-Allele Frequency.
*
Conservation (phastCons): a number between 0 and 1 that describes the degree of sequence conservation among 17 vertebrate species; these numbers are downloaded from the University of California Santa Cruz Genome site (http://genome.ucsc.edu/).
†
Conservation (GERP): The Genomic Evolutionary Rate Profiling (GERP) score was obtained from the GERP website in September of 2011. It ranges from -12.3 to 6.17, with 6.17 being the most conserved.
‡
T2813 & C2814 are replaced by an A, causing a frameshift resulting in a stop codon 12 AA later.