Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24052 | 72379;72380;72381 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| N2AB | 22411 | 67456;67457;67458 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| N2A | 21484 | 64675;64676;64677 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| N2B | 14987 | 45184;45185;45186 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| Novex-1 | 15112 | 45559;45560;45561 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| Novex-2 | 15179 | 45760;45761;45762 | chr2:178573978;178573977;178573976 | chr2:179438705;179438704;179438703 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs777857293  |
0.21 | 0.134 | N | 0.211 | 0.137 | 0.198526703765 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/N | rs777857293 |
0.21 | 0.134 | N | 0.211 | 0.137 | 0.198526703765 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/N | rs777857293 |
0.21 | 0.134 | N | 0.211 | 0.137 | 0.198526703765 | gnomAD-4.0.0 | 2.56354E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78794E-06 | 0 | 0 |
| D/V | None | None | 0.988 | N | 0.572 | 0.447 | 0.695928707293 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1607 | likely_benign | 0.1516 | benign | -0.345 | Destabilizing | 0.704 | D | 0.503 | neutral | N | 0.517145942 | None | None | I |
| D/C | 0.6578 | likely_pathogenic | 0.6055 | pathogenic | 0.079 | Stabilizing | 0.999 | D | 0.574 | neutral | None | None | None | None | I |
| D/E | 0.2112 | likely_benign | 0.187 | benign | -0.498 | Destabilizing | 0.826 | D | 0.407 | neutral | N | 0.468602634 | None | None | I |
| D/F | 0.5111 | ambiguous | 0.4668 | ambiguous | -0.332 | Destabilizing | 0.991 | D | 0.577 | neutral | None | None | None | None | I |
| D/G | 0.2386 | likely_benign | 0.2167 | benign | -0.593 | Destabilizing | 0.826 | D | 0.453 | neutral | N | 0.487618567 | None | None | I |
| D/H | 0.2842 | likely_benign | 0.2364 | benign | -0.533 | Destabilizing | 0.077 | N | 0.331 | neutral | N | 0.496464026 | None | None | I |
| D/I | 0.2968 | likely_benign | 0.2614 | benign | 0.273 | Stabilizing | 0.991 | D | 0.579 | neutral | None | None | None | None | I |
| D/K | 0.4011 | ambiguous | 0.3445 | ambiguous | 0.167 | Stabilizing | 0.884 | D | 0.451 | neutral | None | None | None | None | I |
| D/L | 0.3461 | ambiguous | 0.3037 | benign | 0.273 | Stabilizing | 0.969 | D | 0.563 | neutral | None | None | None | None | I |
| D/M | 0.5355 | ambiguous | 0.4994 | ambiguous | 0.583 | Stabilizing | 0.999 | D | 0.56 | neutral | None | None | None | None | I |
| D/N | 0.117 | likely_benign | 0.1124 | benign | -0.125 | Destabilizing | 0.134 | N | 0.211 | neutral | N | 0.492268927 | None | None | I |
| D/P | 0.901 | likely_pathogenic | 0.8806 | pathogenic | 0.091 | Stabilizing | 0.997 | D | 0.565 | neutral | None | None | None | None | I |
| D/Q | 0.3792 | ambiguous | 0.3222 | benign | -0.085 | Destabilizing | 0.982 | D | 0.473 | neutral | None | None | None | None | I |
| D/R | 0.4168 | ambiguous | 0.3582 | ambiguous | 0.201 | Stabilizing | 0.046 | N | 0.421 | neutral | None | None | None | None | I |
| D/S | 0.1411 | likely_benign | 0.1321 | benign | -0.267 | Destabilizing | 0.373 | N | 0.209 | neutral | None | None | None | None | I |
| D/T | 0.2294 | likely_benign | 0.2047 | benign | -0.074 | Destabilizing | 0.939 | D | 0.463 | neutral | None | None | None | None | I |
| D/V | 0.1807 | likely_benign | 0.1657 | benign | 0.091 | Stabilizing | 0.988 | D | 0.572 | neutral | N | 0.506238302 | None | None | I |
| D/W | 0.8499 | likely_pathogenic | 0.8216 | pathogenic | -0.221 | Destabilizing | 0.999 | D | 0.593 | neutral | None | None | None | None | I |
| D/Y | 0.2096 | likely_benign | 0.178 | benign | -0.096 | Destabilizing | 0.976 | D | 0.576 | neutral | N | 0.487872057 | 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.