Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1294 | 4105;4106;4107 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| N2AB | 1294 | 4105;4106;4107 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| N2A | 1294 | 4105;4106;4107 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| N2B | 1248 | 3967;3968;3969 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| Novex-1 | 1248 | 3967;3968;3969 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| Novex-2 | 1248 | 3967;3968;3969 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
| Novex-3 | 1294 | 4105;4106;4107 | chr2:178779312;178779311;178779310 | chr2:179644039;179644038;179644037 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | rs1233143011  |
0.034 | 0.027 | N | 0.305 | 0.104 | 0.177238962908 | gnomAD-2.1.1 | 1.2E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.81E-05 | None | 0 | 0 | 0 |
| D/A | rs1233143011 |
0.034 | 0.027 | N | 0.305 | 0.104 | 0.177238962908 | gnomAD-4.0.0 | 3.42155E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47866E-05 | 3.31356E-05 |
| D/H | None | None | 0.484 | N | 0.323 | 0.096 | 0.130388298395 | gnomAD-4.0.0 | 6.84313E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99543E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1819 | likely_benign | 0.1794 | benign | -0.366 | Destabilizing | 0.027 | N | 0.305 | neutral | N | 0.414734792 | None | None | I |
| D/C | 0.6508 | likely_pathogenic | 0.6562 | pathogenic | 0.153 | Stabilizing | 0.935 | D | 0.305 | neutral | None | None | None | None | I |
| D/E | 0.1107 | likely_benign | 0.1171 | benign | -0.212 | Destabilizing | None | N | 0.079 | neutral | N | 0.404759609 | None | None | I |
| D/F | 0.5596 | ambiguous | 0.5606 | ambiguous | -0.421 | Destabilizing | 0.791 | D | 0.294 | neutral | None | None | None | None | I |
| D/G | 0.2469 | likely_benign | 0.2377 | benign | -0.52 | Destabilizing | None | N | 0.145 | neutral | N | 0.440709676 | None | None | I |
| D/H | 0.2993 | likely_benign | 0.3108 | benign | -0.237 | Destabilizing | 0.484 | N | 0.323 | neutral | N | 0.450929309 | None | None | I |
| D/I | 0.2871 | likely_benign | 0.2892 | benign | -0.014 | Destabilizing | 0.555 | D | 0.337 | neutral | None | None | None | None | I |
| D/K | 0.4424 | ambiguous | 0.4366 | ambiguous | 0.504 | Stabilizing | 0.081 | N | 0.367 | neutral | None | None | None | None | I |
| D/L | 0.3189 | likely_benign | 0.3268 | benign | -0.014 | Destabilizing | 0.149 | N | 0.353 | neutral | None | None | None | None | I |
| D/M | 0.6014 | likely_pathogenic | 0.6098 | pathogenic | 0.205 | Stabilizing | 0.935 | D | 0.286 | neutral | None | None | None | None | I |
| D/N | 0.1394 | likely_benign | 0.142 | benign | 0.21 | Stabilizing | 0.002 | N | 0.119 | neutral | N | 0.444309131 | None | None | I |
| D/P | 0.8396 | likely_pathogenic | 0.8245 | pathogenic | -0.112 | Destabilizing | 0.555 | D | 0.377 | neutral | None | None | None | None | I |
| D/Q | 0.298 | likely_benign | 0.3108 | benign | 0.217 | Stabilizing | 0.081 | N | 0.317 | neutral | None | None | None | None | I |
| D/R | 0.4604 | ambiguous | 0.4485 | ambiguous | 0.556 | Stabilizing | 0.235 | N | 0.344 | neutral | None | None | None | None | I |
| D/S | 0.1284 | likely_benign | 0.1317 | benign | 0.125 | Stabilizing | 0.007 | N | 0.084 | neutral | None | None | None | None | I |
| D/T | 0.2132 | likely_benign | 0.2219 | benign | 0.251 | Stabilizing | 0.081 | N | 0.363 | neutral | None | None | None | None | I |
| D/V | 0.1856 | likely_benign | 0.1874 | benign | -0.112 | Destabilizing | 0.317 | N | 0.355 | neutral | N | 0.382447208 | None | None | I |
| D/W | 0.8904 | likely_pathogenic | 0.8915 | pathogenic | -0.299 | Destabilizing | 0.935 | D | 0.453 | neutral | None | None | None | None | I |
| D/Y | 0.2744 | likely_benign | 0.2637 | benign | -0.184 | Destabilizing | 0.741 | D | 0.295 | neutral | N | 0.449761029 | 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.