Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32785 | 98578;98579;98580 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| N2AB | 31144 | 93655;93656;93657 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| N2A | 30217 | 90874;90875;90876 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| N2B | 23720 | 71383;71384;71385 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| Novex-1 | 23845 | 71758;71759;71760 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| Novex-2 | 23912 | 71959;71960;71961 | chr2:178539712;178539711;178539710 | chr2:179404439;179404438;179404437 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.22 | N | 0.377 | 0.192 | 0.395441342475 | gnomAD-4.0.0 | 1.36844E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.7989E-06 | 0 | 0 |
| A/V | rs2154140130  |
None | None | N | 0.164 | 0.143 | 0.363158594168 | gnomAD-4.0.0 | 2.05266E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99452E-07 | 2.31863E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.568 | likely_pathogenic | 0.6156 | pathogenic | -0.569 | Destabilizing | 0.909 | D | 0.407 | neutral | None | None | None | None | N |
| A/D | 0.4652 | ambiguous | 0.6128 | pathogenic | -0.867 | Destabilizing | 0.497 | N | 0.479 | neutral | N | 0.436858362 | None | None | N |
| A/E | 0.3761 | ambiguous | 0.5052 | ambiguous | -0.883 | Destabilizing | 0.272 | N | 0.407 | neutral | None | None | None | None | N |
| A/F | 0.4718 | ambiguous | 0.5852 | pathogenic | -0.671 | Destabilizing | 0.567 | D | 0.547 | neutral | None | None | None | None | N |
| A/G | 0.2276 | likely_benign | 0.268 | benign | -0.789 | Destabilizing | 0.22 | N | 0.377 | neutral | N | 0.517916733 | None | None | N |
| A/H | 0.5963 | likely_pathogenic | 0.6931 | pathogenic | -0.848 | Destabilizing | 0.968 | D | 0.551 | neutral | None | None | None | None | N |
| A/I | 0.3102 | likely_benign | 0.4102 | ambiguous | -0.096 | Destabilizing | 0.157 | N | 0.417 | neutral | None | None | None | None | N |
| A/K | 0.5631 | ambiguous | 0.7009 | pathogenic | -0.943 | Destabilizing | 0.567 | D | 0.411 | neutral | None | None | None | None | N |
| A/L | 0.2567 | likely_benign | 0.3347 | benign | -0.096 | Destabilizing | 0.072 | N | 0.428 | neutral | None | None | None | None | N |
| A/M | 0.2326 | likely_benign | 0.2943 | benign | -0.238 | Destabilizing | 0.726 | D | 0.465 | neutral | None | None | None | None | N |
| A/N | 0.3122 | likely_benign | 0.4145 | ambiguous | -0.71 | Destabilizing | 0.567 | D | 0.523 | neutral | None | None | None | None | N |
| A/P | 0.5637 | ambiguous | 0.6929 | pathogenic | -0.212 | Destabilizing | 0.667 | D | 0.433 | neutral | N | 0.469874857 | None | None | N |
| A/Q | 0.4334 | ambiguous | 0.5188 | ambiguous | -0.824 | Destabilizing | 0.726 | D | 0.457 | neutral | None | None | None | None | N |
| A/R | 0.5155 | ambiguous | 0.6417 | pathogenic | -0.618 | Destabilizing | 0.567 | D | 0.442 | neutral | None | None | None | None | N |
| A/S | 0.1191 | likely_benign | 0.1392 | benign | -0.99 | Destabilizing | 0.124 | N | 0.436 | neutral | N | 0.379367496 | None | None | N |
| A/T | 0.1052 | likely_benign | 0.1428 | benign | -0.912 | Destabilizing | None | N | 0.163 | neutral | N | 0.38507996 | None | None | N |
| A/V | 0.1585 | likely_benign | 0.2034 | benign | -0.212 | Destabilizing | None | N | 0.164 | neutral | N | 0.434684848 | None | None | N |
| A/W | 0.8286 | likely_pathogenic | 0.8845 | pathogenic | -1.036 | Destabilizing | 0.968 | D | 0.685 | prob.neutral | None | None | None | None | N |
| A/Y | 0.5931 | likely_pathogenic | 0.6853 | pathogenic | -0.598 | Destabilizing | 0.726 | D | 0.555 | 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.