Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14526 | 43801;43802;43803 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| N2AB | 12885 | 38878;38879;38880 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| N2A | 11958 | 36097;36098;36099 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| N2B | 5461 | 16606;16607;16608 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| Novex-1 | 5586 | 16981;16982;16983 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| Novex-2 | 5653 | 17182;17183;17184 | chr2:178632318;178632317;178632316 | chr2:179497045;179497044;179497043 |
| 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/L | rs373491468  |
0.527 | None | N | 0.289 | 0.263 | 0.128392430309 | gnomAD-2.1.1 | 1.26E-05 | None | None | None | None | N | None | 6.86E-05 | 0 | None | 0 | 0 | None | 3.42E-05 | None | 0 | 9.31E-06 | 0 |
| R/L | rs373491468 |
0.527 | None | N | 0.289 | 0.263 | 0.128392430309 | gnomAD-4.0.0 | 1.37382E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.01717E-07 | 1.17327E-05 | 0 |
| R/Q | None | 0.137 | 0.003 | N | 0.261 | 0.16 | None | gnomAD-2.1.1 | 1.03826E-04 | None | None | None | None | N | None | 8.59E-05 | 8.78E-05 | None | 0 | 0 | None | 3.42E-05 | None | 0 | 1.70879E-04 | 1.44175E-04 |
| R/Q | None | 0.137 | 0.003 | N | 0.261 | 0.16 | None | gnomAD-3.1.2 | 1.71127E-04 | None | None | None | None | N | None | 1.69221E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.79486E-04 | 0 | 0 |
| R/Q | None | 0.137 | 0.003 | N | 0.261 | 0.16 | None | gnomAD-4.0.0 | 2.81142E-04 | None | None | None | None | N | None | 1.33761E-04 | 8.44652E-05 | None | 0 | 0 | None | 0 | 0 | 3.46651E-04 | 2.22089E-05 | 4.33805E-04 |
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 | 0.2125 | likely_benign | 0.1614 | benign | 0.091 | Stabilizing | 0.004 | N | 0.301 | neutral | None | None | None | None | N |
| R/C | 0.1621 | likely_benign | 0.1236 | benign | -0.272 | Destabilizing | 0.497 | N | 0.395 | neutral | None | None | None | None | N |
| R/D | 0.3977 | ambiguous | 0.2863 | benign | -0.378 | Destabilizing | 0.018 | N | 0.413 | neutral | None | None | None | None | N |
| R/E | 0.2635 | likely_benign | 0.2119 | benign | -0.334 | Destabilizing | 0.009 | N | 0.305 | neutral | None | None | None | None | N |
| R/F | 0.4204 | ambiguous | 0.3294 | benign | -0.235 | Destabilizing | 0.074 | N | 0.519 | neutral | None | None | None | None | N |
| R/G | 0.1806 | likely_benign | 0.1337 | benign | -0.044 | Destabilizing | 0.035 | N | 0.335 | neutral | N | 0.418669997 | None | None | N |
| R/H | 0.0949 | likely_benign | 0.0789 | benign | -0.585 | Destabilizing | None | N | 0.297 | neutral | None | None | None | None | N |
| R/I | 0.233 | likely_benign | 0.1944 | benign | 0.401 | Stabilizing | 0.022 | N | 0.485 | neutral | None | None | None | None | N |
| R/K | 0.1199 | likely_benign | 0.1068 | benign | -0.168 | Destabilizing | 0.004 | N | 0.304 | neutral | None | None | None | None | N |
| R/L | 0.1527 | likely_benign | 0.1242 | benign | 0.401 | Stabilizing | None | N | 0.289 | neutral | N | 0.341917028 | None | None | N |
| R/M | 0.2693 | likely_benign | 0.2256 | benign | -0.116 | Destabilizing | 0.138 | N | 0.445 | neutral | None | None | None | None | N |
| R/N | 0.3434 | ambiguous | 0.254 | benign | -0.147 | Destabilizing | 0.009 | N | 0.435 | neutral | None | None | None | None | N |
| R/P | 0.1287 | likely_benign | 0.0963 | benign | 0.315 | Stabilizing | None | N | 0.255 | neutral | N | 0.255283631 | None | None | N |
| R/Q | 0.1047 | likely_benign | 0.0902 | benign | -0.144 | Destabilizing | 0.003 | N | 0.261 | neutral | N | 0.348145268 | None | None | N |
| R/S | 0.2869 | likely_benign | 0.2107 | benign | -0.255 | Destabilizing | 0.009 | N | 0.31 | neutral | None | None | None | None | N |
| R/T | 0.1804 | likely_benign | 0.1414 | benign | -0.108 | Destabilizing | None | N | 0.231 | neutral | None | None | None | None | N |
| R/V | 0.273 | likely_benign | 0.2215 | benign | 0.315 | Stabilizing | 0.009 | N | 0.345 | neutral | None | None | None | None | N |
| R/W | 0.1624 | likely_benign | 0.1343 | benign | -0.458 | Destabilizing | 0.788 | D | 0.396 | neutral | None | None | None | None | N |
| R/Y | 0.2937 | likely_benign | 0.2223 | benign | -0.049 | Destabilizing | 0.022 | N | 0.543 | neutral | None | None | None | None | N |
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.