Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3948 | 12067;12068;12069 | chr2:178741391;178741390;178741389 | chr2:179606118;179606117;179606116 |
| N2AB | 3631 | 11116;11117;11118 | chr2:178741391;178741390;178741389 | chr2:179606118;179606117;179606116 |
| N2A | None | None | chr2:None | chr2:None |
| N2B | 3585 | 10978;10979;10980 | chr2:178741391;178741390;178741389 | chr2:179606118;179606117;179606116 |
| Novex-1 | 3710 | 11353;11354;11355 | chr2:178741391;178741390;178741389 | chr2:179606118;179606117;179606116 |
| Novex-2 | 3777 | 11554;11555;11556 | chr2:178741391;178741390;178741389 | chr2:179606118;179606117;179606116 |
| Novex-3 | None | None | chr2:None | chr2:None |
Information
Reported SAVs
| SNV | RS | DUET |
PolyPhen-2 |
Condel |
Rhapsody |
REVEL |
MVP |
Source |
MAF |
Disease |
Zygosity |
Site annotation |
mCSM PPI |
Predicted PPI site |
Comments |
AFR |
AMR |
AMS |
ASJ |
EAS |
EUR |
FIN |
MDE |
NFE |
SAS |
OTH |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs397517827  |
-0.08 | 0.964 | D | 0.347 | 0.215 | None | gnomAD-2.1.1 | 2.05215E-04 | None | None | None | None | I | None | 1.29199E-04 | 2.9E-05 | None | 0 | 7.2367E-04 | None | 1.04575E-03 | None | 0 | 2.67E-05 | 0 |
| R/C | rs397517827 |
-0.08 | 0.964 | D | 0.347 | 0.215 | None | gnomAD-3.1.2 | 1.18314E-04 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 9.65624E-04 | None | 0 | 0 | 1.47E-05 | 2.27838E-03 | 0 |
| R/C | rs397517827 |
-0.08 | 0.964 | D | 0.347 | 0.215 | None | gnomAD-4.0.0 | 1.31981E-04 | None | None | None | None | I | None | 5.33063E-05 | 0 | None | 0 | 4.45812E-04 | None | 0 | 1.64962E-04 | 3.89887E-05 | 1.4713E-03 | 1.28053E-04 |
| R/G | None | None | 0.13 | D | 0.444 | 0.175 | None | gnomAD-4.0.0 | 6.84175E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99429E-07 | 0 | 0 |
| R/H | rs775618077 |
-0.537 | None | N | 0.209 | 0.067 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 0 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 1.99888E-04 | 3.13E-05 | 1.4041E-04 |
| R/H | rs775618077 |
-0.537 | None | N | 0.209 | 0.067 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 1.31044E-04 | 0 | 0 | 0 | None | 9.44E-05 | 0 | 1.47E-05 | 0 | 0 |
| R/H | rs775618077 |
-0.537 | None | N | 0.209 | 0.067 | None | gnomAD-4.0.0 | 1.98304E-05 | None | None | None | None | I | None | 0 | 8.33583E-05 | None | 0 | 2.22826E-05 | None | 1.40647E-04 | 0 | 1.35614E-05 | 0 | 1.60128E-05 |
| R/L | rs775618077 |
None | None | N | 0.253 | 0.091 | None | gnomAD-4.0.0 | 4.10505E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39659E-06 | 0 | 0 |
Saturation Mutagenesis
SAV |
AlphaMissense (IC) |
AlphaMissense Class (IC) |
AlphaMissense (N2AB) |
AlphaMissense Class (N2AB) |
mCSM |
mCSM class |
PolyPhen-2 |
PolyPhen-2 Class |
Rhapsody |
Rhapsody Class |
Condel |
Condel Score |
Site annotation |
mCSM PPI |
Predicted PPI site |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2167 | likely_benign | 0.1965 | benign | 0.01 | Stabilizing | 0.016 | N | 0.398 | neutral | None | None | None | None | I |
| R/C | 0.0748 | likely_benign | 0.0705 | benign | -0.262 | Destabilizing | 0.964 | D | 0.347 | neutral | D | 0.577588989 | None | None | I |
| R/D | 0.3085 | likely_benign | 0.3007 | benign | -0.084 | Destabilizing | 0.072 | N | 0.494 | neutral | None | None | None | None | I |
| R/E | 0.2234 | likely_benign | 0.1969 | benign | -0.001 | Destabilizing | 0.016 | N | 0.384 | neutral | None | None | None | None | I |
| R/F | 0.2356 | likely_benign | 0.2165 | benign | -0.165 | Destabilizing | 0.12 | N | 0.409 | neutral | None | None | None | None | I |
| R/G | 0.1452 | likely_benign | 0.1408 | benign | -0.203 | Destabilizing | 0.13 | N | 0.444 | neutral | D | 0.550660228 | None | None | I |
| R/H | 0.0633 | likely_benign | 0.0617 | benign | -0.698 | Destabilizing | None | N | 0.209 | neutral | N | 0.477420649 | None | None | I |
| R/I | 0.1485 | likely_benign | 0.1304 | benign | 0.536 | Stabilizing | 0.038 | N | 0.466 | neutral | None | None | None | None | I |
| R/K | 0.1365 | likely_benign | 0.1257 | benign | -0.089 | Destabilizing | 0.016 | N | 0.385 | neutral | None | None | None | None | I |
| R/L | 0.1186 | likely_benign | 0.1045 | benign | 0.536 | Stabilizing | None | N | 0.253 | neutral | N | 0.502592331 | None | None | I |
| R/M | 0.2469 | likely_benign | 0.2188 | benign | -0.015 | Destabilizing | 0.214 | N | 0.411 | neutral | None | None | None | None | I |
| R/N | 0.245 | likely_benign | 0.2353 | benign | 0.015 | Stabilizing | 0.038 | N | 0.411 | neutral | None | None | None | None | I |
| R/P | 0.3266 | likely_benign | 0.3143 | benign | 0.382 | Stabilizing | 0.515 | D | 0.458 | neutral | N | 0.511314617 | None | None | I |
| R/Q | 0.0879 | likely_benign | 0.0811 | benign | -0.022 | Destabilizing | None | N | 0.217 | neutral | None | None | None | None | I |
| R/S | 0.189 | likely_benign | 0.1744 | benign | -0.317 | Destabilizing | 0.03 | N | 0.414 | neutral | N | 0.48408601 | None | None | I |
| R/T | 0.1467 | likely_benign | 0.1287 | benign | -0.088 | Destabilizing | 0.072 | N | 0.477 | neutral | None | None | None | None | I |
| R/V | 0.1956 | likely_benign | 0.1723 | benign | 0.382 | Stabilizing | 0.038 | N | 0.495 | neutral | None | None | None | None | I |
| R/W | 0.1195 | likely_benign | 0.1066 | benign | -0.226 | Destabilizing | 0.864 | D | 0.349 | neutral | None | None | None | None | I |
| R/Y | 0.1342 | likely_benign | 0.1302 | benign | 0.188 | Stabilizing | 0.038 | N | 0.463 | neutral | None | None | None | None | I |
Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.