Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17328 | 52207;52208;52209 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| N2AB | 15687 | 47284;47285;47286 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| N2A | 14760 | 44503;44504;44505 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| N2B | 8263 | 25012;25013;25014 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| Novex-1 | 8388 | 25387;25388;25389 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| Novex-2 | 8455 | 25588;25589;25590 | chr2:178609328;178609327;178609326 | chr2:179474055;179474054;179474053 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/Q | rs371827403  |
0.18 | None | N | 0.193 | 0.087 | None | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 6.48E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/Q | rs371827403 |
0.18 | None | N | 0.193 | 0.087 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/Q | rs371827403 |
0.18 | None | N | 0.193 | 0.087 | None | gnomAD-4.0.0 | 2.57267E-06 | None | None | None | None | N | None | 1.69779E-05 | 0 | None | 0 | 2.44093E-05 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs1268313785 |
None | None | N | 0.243 | 0.03 | 0.18274738541 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| K/R | rs1268313785 |
None | None | N | 0.243 | 0.03 | 0.18274738541 | gnomAD-4.0.0 | 2.03033E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.20509E-06 | 0 | 3.40321E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.2917 | likely_benign | 0.2895 | benign | -0.015 | Destabilizing | 0.016 | N | 0.396 | neutral | None | None | None | None | N |
| K/C | 0.5433 | ambiguous | 0.5105 | ambiguous | -0.248 | Destabilizing | 0.864 | D | 0.253 | neutral | None | None | None | None | N |
| K/D | 0.5505 | ambiguous | 0.5718 | pathogenic | 0.039 | Stabilizing | 0.072 | N | 0.427 | neutral | None | None | None | None | N |
| K/E | 0.157 | likely_benign | 0.1638 | benign | 0.021 | Stabilizing | 0.012 | N | 0.377 | neutral | N | 0.436331847 | None | None | N |
| K/F | 0.6772 | likely_pathogenic | 0.6489 | pathogenic | -0.379 | Destabilizing | 0.356 | N | 0.295 | neutral | None | None | None | None | N |
| K/G | 0.3722 | ambiguous | 0.3655 | ambiguous | -0.16 | Destabilizing | 0.072 | N | 0.367 | neutral | None | None | None | None | N |
| K/H | 0.2698 | likely_benign | 0.2627 | benign | -0.45 | Destabilizing | None | N | 0.259 | neutral | None | None | None | None | N |
| K/I | 0.2734 | likely_benign | 0.2758 | benign | 0.279 | Stabilizing | 0.171 | N | 0.338 | neutral | N | 0.474679591 | None | None | N |
| K/L | 0.2881 | likely_benign | 0.2705 | benign | 0.279 | Stabilizing | 0.072 | N | 0.387 | neutral | None | None | None | None | N |
| K/M | 0.2381 | likely_benign | 0.2431 | benign | 0.175 | Stabilizing | 0.356 | N | 0.331 | neutral | None | None | None | None | N |
| K/N | 0.398 | ambiguous | 0.4346 | ambiguous | 0.252 | Stabilizing | 0.055 | N | 0.364 | neutral | N | 0.45634176 | None | None | N |
| K/P | 0.7844 | likely_pathogenic | 0.6936 | pathogenic | 0.206 | Stabilizing | 0.356 | N | 0.415 | neutral | None | None | None | None | N |
| K/Q | 0.1047 | likely_benign | 0.1046 | benign | 0.043 | Stabilizing | None | N | 0.193 | neutral | N | 0.473986158 | None | None | N |
| K/R | 0.0718 | likely_benign | 0.0694 | benign | 0.019 | Stabilizing | None | N | 0.243 | neutral | N | 0.473639441 | None | None | N |
| K/S | 0.3666 | ambiguous | 0.3671 | ambiguous | -0.219 | Destabilizing | 0.016 | N | 0.347 | neutral | None | None | None | None | N |
| K/T | 0.1765 | likely_benign | 0.1875 | benign | -0.105 | Destabilizing | 0.001 | N | 0.238 | neutral | N | 0.462769087 | None | None | N |
| K/V | 0.2375 | likely_benign | 0.2377 | benign | 0.206 | Stabilizing | 0.072 | N | 0.415 | neutral | None | None | None | None | N |
| K/W | 0.656 | likely_pathogenic | 0.601 | pathogenic | -0.407 | Destabilizing | 0.864 | D | 0.256 | neutral | None | None | None | None | N |
| K/Y | 0.5704 | likely_pathogenic | 0.5439 | ambiguous | -0.035 | Destabilizing | 0.214 | N | 0.372 | 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.