Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17915 | 53968;53969;53970 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| N2AB | 16274 | 49045;49046;49047 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| N2A | 15347 | 46264;46265;46266 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| N2B | 8850 | 26773;26774;26775 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| Novex-1 | 8975 | 27148;27149;27150 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| Novex-2 | 9042 | 27349;27350;27351 | chr2:178605552;178605551;178605550 | chr2:179470279;179470278;179470277 |
| 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 | None | None | 0.251 | N | 0.461 | 0.181 | 0.282179105231 | gnomAD-4.0.0 | 1.5942E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43488E-05 | 0 |
| R/Q | rs758896047  |
0.464 | 0.01 | N | 0.251 | 0.1 | 0.0884992946249 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| R/Q | rs758896047 |
0.464 | 0.01 | N | 0.251 | 0.1 | 0.0884992946249 | gnomAD-3.1.2 | 5.93E-05 | None | None | None | None | N | None | 4.84E-05 | 3.9427E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07555E-04 | 0 |
| R/Q | rs758896047 |
0.464 | 0.01 | N | 0.251 | 0.1 | 0.0884992946249 | gnomAD-4.0.0 | 2.56717E-05 | None | None | None | None | N | None | 3.39236E-05 | 1.52729E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 2.6842E-05 | 1.99476E-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 | 0.1562 | likely_benign | 0.1698 | benign | 0.057 | Stabilizing | 0.067 | N | 0.419 | neutral | None | None | None | None | N |
| R/C | 0.12 | likely_benign | 0.1204 | benign | -0.21 | Destabilizing | 0.935 | D | 0.285 | neutral | None | None | None | None | N |
| R/D | 0.2155 | likely_benign | 0.2386 | benign | -0.299 | Destabilizing | 0.035 | N | 0.39 | neutral | None | None | None | None | N |
| R/E | 0.1359 | likely_benign | 0.1451 | benign | -0.264 | Destabilizing | 0.001 | N | 0.161 | neutral | None | None | None | None | N |
| R/F | 0.2624 | likely_benign | 0.264 | benign | -0.281 | Destabilizing | 0.38 | N | 0.323 | neutral | None | None | None | None | N |
| R/G | 0.1298 | likely_benign | 0.1398 | benign | -0.071 | Destabilizing | 0.251 | N | 0.407 | neutral | N | 0.427803656 | None | None | N |
| R/H | 0.074 | likely_benign | 0.0757 | benign | -0.575 | Destabilizing | 0.001 | N | 0.211 | neutral | None | None | None | None | N |
| R/I | 0.1219 | likely_benign | 0.1239 | benign | 0.345 | Stabilizing | 0.555 | D | 0.355 | neutral | None | None | None | None | N |
| R/K | 0.0745 | likely_benign | 0.085 | benign | -0.135 | Destabilizing | 0.035 | N | 0.306 | neutral | None | None | None | None | N |
| R/L | 0.1261 | likely_benign | 0.1242 | benign | 0.345 | Stabilizing | 0.251 | N | 0.461 | neutral | N | 0.452333954 | None | None | N |
| R/M | 0.1361 | likely_benign | 0.1493 | benign | -0.073 | Destabilizing | 0.555 | D | 0.361 | neutral | None | None | None | None | N |
| R/N | 0.1784 | likely_benign | 0.1734 | benign | -0.037 | Destabilizing | 0.081 | N | 0.359 | neutral | None | None | None | None | N |
| R/P | 0.545 | ambiguous | 0.5091 | ambiguous | 0.266 | Stabilizing | 0.705 | D | 0.413 | neutral | N | 0.475941533 | None | None | N |
| R/Q | 0.0692 | likely_benign | 0.0721 | benign | -0.072 | Destabilizing | 0.01 | N | 0.251 | neutral | N | 0.436825784 | None | None | N |
| R/S | 0.1664 | likely_benign | 0.1817 | benign | -0.196 | Destabilizing | 0.067 | N | 0.401 | neutral | None | None | None | None | N |
| R/T | 0.0928 | likely_benign | 0.0963 | benign | -0.062 | Destabilizing | 0.149 | N | 0.455 | neutral | None | None | None | None | N |
| R/V | 0.1338 | likely_benign | 0.1386 | benign | 0.266 | Stabilizing | 0.262 | N | 0.419 | neutral | None | None | None | None | N |
| R/W | 0.1387 | likely_benign | 0.1443 | benign | -0.485 | Destabilizing | 0.935 | D | 0.279 | neutral | None | None | None | None | N |
| R/Y | 0.1774 | likely_benign | 0.1769 | benign | -0.08 | Destabilizing | 0.235 | N | 0.396 | 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.