Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32622 | 98089;98090;98091 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| N2AB | 30981 | 93166;93167;93168 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| N2A | 30054 | 90385;90386;90387 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| N2B | 23557 | 70894;70895;70896 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| Novex-1 | 23682 | 71269;71270;71271 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| Novex-2 | 23749 | 71470;71471;71472 | chr2:178540302;178540301;178540300 | chr2:179405029;179405028;179405027 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs777613491  |
-1.143 | 0.999 | N | 0.57 | 0.328 | 0.281381271821 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 6.46E-05 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| S/N | rs777613491 |
-1.143 | 0.999 | N | 0.57 | 0.328 | 0.281381271821 | gnomAD-4.0.0 | 3.4211E-06 | None | None | None | None | N | None | 2.98864E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79901E-06 | 1.15931E-05 | 1.65656E-05 |
| S/R | rs1693783510 |
None | 0.999 | N | 0.689 | 0.376 | 0.223146558224 | gnomAD-4.0.0 | 1.59133E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02425E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0927 | likely_benign | 0.0967 | benign | -0.517 | Destabilizing | 0.982 | D | 0.439 | neutral | None | None | None | None | N |
| S/C | 0.1424 | likely_benign | 0.1467 | benign | -0.531 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | N | 0.48176772 | None | None | N |
| S/D | 0.3265 | likely_benign | 0.3196 | benign | -1.246 | Destabilizing | 0.999 | D | 0.566 | neutral | None | None | None | None | N |
| S/E | 0.4641 | ambiguous | 0.4558 | ambiguous | -1.124 | Destabilizing | 0.998 | D | 0.551 | neutral | None | None | None | None | N |
| S/F | 0.263 | likely_benign | 0.2964 | benign | -0.359 | Destabilizing | 0.996 | D | 0.709 | prob.delet. | None | None | None | None | N |
| S/G | 0.1025 | likely_benign | 0.0949 | benign | -0.889 | Destabilizing | 0.997 | D | 0.479 | neutral | N | 0.484217086 | None | None | N |
| S/H | 0.378 | ambiguous | 0.3723 | ambiguous | -1.477 | Destabilizing | 1.0 | D | 0.681 | prob.neutral | None | None | None | None | N |
| S/I | 0.2331 | likely_benign | 0.2377 | benign | 0.396 | Stabilizing | 0.961 | D | 0.621 | neutral | N | 0.469486361 | None | None | N |
| S/K | 0.6789 | likely_pathogenic | 0.6831 | pathogenic | -0.8 | Destabilizing | 0.998 | D | 0.545 | neutral | None | None | None | None | N |
| S/L | 0.1309 | likely_benign | 0.1469 | benign | 0.396 | Stabilizing | 0.08 | N | 0.36 | neutral | None | None | None | None | N |
| S/M | 0.2074 | likely_benign | 0.2067 | benign | 0.417 | Stabilizing | 0.996 | D | 0.702 | prob.neutral | None | None | None | None | N |
| S/N | 0.1166 | likely_benign | 0.1114 | benign | -1.232 | Destabilizing | 0.999 | D | 0.57 | neutral | N | 0.468631559 | None | None | N |
| S/P | 0.8161 | likely_pathogenic | 0.8364 | pathogenic | 0.129 | Stabilizing | 0.999 | D | 0.69 | prob.neutral | None | None | None | None | N |
| S/Q | 0.4799 | ambiguous | 0.4611 | ambiguous | -1.062 | Destabilizing | 0.999 | D | 0.579 | neutral | None | None | None | None | N |
| S/R | 0.6225 | likely_pathogenic | 0.6496 | pathogenic | -1.024 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | N | 0.495644801 | None | None | N |
| S/T | 0.0919 | likely_benign | 0.095 | benign | -0.911 | Destabilizing | 0.99 | D | 0.489 | neutral | N | 0.482963506 | None | None | N |
| S/V | 0.2251 | likely_benign | 0.2255 | benign | 0.129 | Stabilizing | 0.971 | D | 0.575 | neutral | None | None | None | None | N |
| S/W | 0.4203 | ambiguous | 0.4706 | ambiguous | -0.638 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | N |
| S/Y | 0.2391 | likely_benign | 0.2648 | benign | -0.242 | Destabilizing | 0.999 | D | 0.747 | deleterious | 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.