Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29084 | 87475;87476;87477 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| N2AB | 27443 | 82552;82553;82554 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| N2A | 26516 | 79771;79772;79773 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| N2B | 20019 | 60280;60281;60282 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| Novex-1 | 20144 | 60655;60656;60657 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| Novex-2 | 20211 | 60856;60857;60858 | chr2:178558104;178558103;178558102 | chr2:179422831;179422830;179422829 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/H | rs370776552  |
0.111 | 0.794 | D | 0.342 | 0.231 | None | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 1.66058E-04 |
| P/H | rs370776552 |
0.111 | 0.794 | D | 0.342 | 0.231 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| P/H | rs370776552 |
0.111 | 0.794 | D | 0.342 | 0.231 | None | gnomAD-4.0.0 | 6.1969E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.5627E-05 | 0 | 7.62824E-06 | 0 | 0 |
| P/L | None | None | 0.002 | N | 0.258 | 0.185 | 0.464183351471 | gnomAD-4.0.0 | 6.84174E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99429E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0596 | likely_benign | 0.0614 | benign | -0.381 | Destabilizing | 0.001 | N | 0.153 | neutral | N | 0.467815987 | None | None | N |
| P/C | 0.2726 | likely_benign | 0.3152 | benign | -0.561 | Destabilizing | 0.951 | D | 0.348 | neutral | None | None | None | None | N |
| P/D | 0.3185 | likely_benign | 0.3499 | ambiguous | -0.073 | Destabilizing | 0.418 | N | 0.317 | neutral | None | None | None | None | N |
| P/E | 0.2153 | likely_benign | 0.2434 | benign | -0.186 | Destabilizing | 0.129 | N | 0.317 | neutral | None | None | None | None | N |
| P/F | 0.2253 | likely_benign | 0.273 | benign | -0.617 | Destabilizing | 0.716 | D | 0.385 | neutral | None | None | None | None | N |
| P/G | 0.2161 | likely_benign | 0.2438 | benign | -0.51 | Destabilizing | 0.129 | N | 0.343 | neutral | None | None | None | None | N |
| P/H | 0.1333 | likely_benign | 0.1517 | benign | -0.132 | Destabilizing | 0.794 | D | 0.342 | neutral | D | 0.530808673 | None | None | N |
| P/I | 0.1092 | likely_benign | 0.1362 | benign | -0.192 | Destabilizing | 0.264 | N | 0.377 | neutral | None | None | None | None | N |
| P/K | 0.2308 | likely_benign | 0.2688 | benign | -0.33 | Destabilizing | 0.264 | N | 0.317 | neutral | None | None | None | None | N |
| P/L | 0.0642 | likely_benign | 0.0718 | benign | -0.192 | Destabilizing | 0.002 | N | 0.258 | neutral | N | 0.471299009 | None | None | N |
| P/M | 0.1427 | likely_benign | 0.163 | benign | -0.289 | Destabilizing | 0.716 | D | 0.359 | neutral | None | None | None | None | N |
| P/N | 0.1742 | likely_benign | 0.2021 | benign | -0.045 | Destabilizing | 0.264 | N | 0.39 | neutral | None | None | None | None | N |
| P/Q | 0.1057 | likely_benign | 0.1209 | benign | -0.27 | Destabilizing | 0.027 | N | 0.199 | neutral | None | None | None | None | N |
| P/R | 0.1785 | likely_benign | 0.1961 | benign | 0.133 | Stabilizing | 0.351 | N | 0.373 | neutral | N | 0.481900005 | None | None | N |
| P/S | 0.0845 | likely_benign | 0.0918 | benign | -0.425 | Destabilizing | 0.002 | N | 0.193 | neutral | N | 0.492423643 | None | None | N |
| P/T | 0.0699 | likely_benign | 0.079 | benign | -0.435 | Destabilizing | 0.001 | N | 0.154 | neutral | N | 0.478032981 | None | None | N |
| P/V | 0.0917 | likely_benign | 0.1024 | benign | -0.22 | Destabilizing | 0.01 | N | 0.219 | neutral | None | None | None | None | N |
| P/W | 0.4336 | ambiguous | 0.4972 | ambiguous | -0.706 | Destabilizing | 0.983 | D | 0.383 | neutral | None | None | None | None | N |
| P/Y | 0.2558 | likely_benign | 0.307 | benign | -0.396 | Destabilizing | 0.836 | D | 0.369 | 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.