Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2455 | 7588;7589;7590 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| N2AB | 2455 | 7588;7589;7590 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| N2A | 2455 | 7588;7589;7590 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| N2B | 2409 | 7450;7451;7452 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| Novex-1 | 2409 | 7450;7451;7452 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| Novex-2 | 2409 | 7450;7451;7452 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
| Novex-3 | 2455 | 7588;7589;7590 | chr2:178773693;178773692;178773691 | chr2:179638420;179638419;179638418 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | None | None | None | N | 0.183 | 0.142 | 0.215109475489 | gnomAD-4.0.0 | 1.36822E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79864E-06 | 0 | 0 |
| N/H | rs1561255734  |
None | None | N | 0.183 | 0.134 | 0.20549828249 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| N/H | rs1561255734 |
None | None | N | 0.183 | 0.134 | 0.20549828249 | gnomAD-4.0.0 | 6.84111E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99321E-07 | 0 | 0 |
| N/S | rs2091854692 |
None | None | N | 0.157 | 0.072 | 0.101711395817 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| N/S | rs2091854692 |
None | None | N | 0.157 | 0.072 | 0.101711395817 | gnomAD-4.0.0 | 3.84202E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 7.17576E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1443 | likely_benign | 0.1406 | benign | -0.243 | Destabilizing | 0.007 | N | 0.265 | neutral | None | None | None | None | N |
| N/C | 0.1944 | likely_benign | 0.1972 | benign | 0.255 | Stabilizing | 0.676 | D | 0.26 | neutral | None | None | None | None | N |
| N/D | 0.0982 | likely_benign | 0.0952 | benign | 0.188 | Stabilizing | None | N | 0.183 | neutral | N | 0.493644121 | None | None | N |
| N/E | 0.2215 | likely_benign | 0.2157 | benign | 0.142 | Stabilizing | 0.016 | N | 0.216 | neutral | None | None | None | None | N |
| N/F | 0.4037 | ambiguous | 0.3955 | ambiguous | -0.725 | Destabilizing | 0.356 | N | 0.333 | neutral | None | None | None | None | N |
| N/G | 0.2346 | likely_benign | 0.2289 | benign | -0.383 | Destabilizing | 0.016 | N | 0.204 | neutral | None | None | None | None | N |
| N/H | 0.0689 | likely_benign | 0.0693 | benign | -0.407 | Destabilizing | None | N | 0.183 | neutral | N | 0.463289778 | None | None | N |
| N/I | 0.1643 | likely_benign | 0.1586 | benign | 0.028 | Stabilizing | 0.055 | N | 0.369 | neutral | N | 0.488120565 | None | None | N |
| N/K | 0.1574 | likely_benign | 0.1521 | benign | 0.182 | Stabilizing | 0.012 | N | 0.187 | neutral | N | 0.481934572 | None | None | N |
| N/L | 0.1838 | likely_benign | 0.1803 | benign | 0.028 | Stabilizing | 0.038 | N | 0.328 | neutral | None | None | None | None | N |
| N/M | 0.2494 | likely_benign | 0.2424 | benign | 0.251 | Stabilizing | 0.356 | N | 0.271 | neutral | None | None | None | None | N |
| N/P | 0.4445 | ambiguous | 0.433 | ambiguous | -0.037 | Destabilizing | 0.072 | N | 0.384 | neutral | None | None | None | None | N |
| N/Q | 0.2045 | likely_benign | 0.2013 | benign | -0.312 | Destabilizing | 0.072 | N | 0.209 | neutral | None | None | None | None | N |
| N/R | 0.1774 | likely_benign | 0.1732 | benign | 0.23 | Stabilizing | 0.072 | N | 0.207 | neutral | None | None | None | None | N |
| N/S | 0.0696 | likely_benign | 0.0694 | benign | -0.077 | Destabilizing | None | N | 0.157 | neutral | N | 0.411761879 | None | None | N |
| N/T | 0.0806 | likely_benign | 0.079 | benign | 0.014 | Stabilizing | None | N | 0.173 | neutral | N | 0.406011901 | None | None | N |
| N/V | 0.1665 | likely_benign | 0.1604 | benign | -0.037 | Destabilizing | 0.038 | N | 0.367 | neutral | None | None | None | None | N |
| N/W | 0.6417 | likely_pathogenic | 0.6348 | pathogenic | -0.76 | Destabilizing | 0.864 | D | 0.273 | neutral | None | None | None | None | N |
| N/Y | 0.1282 | likely_benign | 0.1287 | benign | -0.461 | Destabilizing | 0.055 | N | 0.372 | neutral | N | 0.510265694 | 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.