Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18031 | 54316;54317;54318 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| N2AB | 16390 | 49393;49394;49395 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| N2A | 15463 | 46612;46613;46614 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| N2B | 8966 | 27121;27122;27123 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| Novex-1 | 9091 | 27496;27497;27498 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| Novex-2 | 9158 | 27697;27698;27699 | chr2:178605086;178605085;178605084 | chr2:179469813;179469812;179469811 |
| 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/C | None | None | 0.915 | N | 0.653 | 0.26 | 0.408853032482 | gnomAD-4.0.0 | 6.84583E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99866E-07 | 0 | 0 |
| S/G | rs397517615  |
-1.107 | 0.211 | N | 0.641 | 0.122 | 0.243398259712 | gnomAD-2.1.1 | 8.07E-06 | None | None | None | None | N | None | 6.47E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.66058E-04 |
| S/G | rs397517615 |
-1.107 | 0.211 | N | 0.641 | 0.122 | 0.243398259712 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 0 | 3.93856E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs397517615 |
-1.107 | 0.211 | N | 0.641 | 0.122 | 0.243398259712 | gnomAD-4.0.0 | 8.0608E-06 | None | None | None | None | N | None | 1.33615E-05 | 1.0011E-04 | None | 0 | 0 | None | 0 | 0 | 1.69603E-06 | 0 | 6.4082E-05 |
| S/T | rs1259446367 |
-0.655 | 0.002 | N | 0.528 | 0.116 | 0.0806252709748 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 6.47E-05 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| S/T | rs1259446367 |
-0.655 | 0.002 | N | 0.528 | 0.116 | 0.0806252709748 | gnomAD-4.0.0 | 4.78001E-06 | None | None | None | None | N | None | 5.67537E-05 | 2.28749E-05 | None | 0 | 0 | None | 0 | 0 | 2.86243E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.074 | likely_benign | 0.0718 | benign | -0.69 | Destabilizing | 0.067 | N | 0.582 | neutral | None | None | None | None | N |
| S/C | 0.071 | likely_benign | 0.073 | benign | -0.756 | Destabilizing | 0.915 | D | 0.653 | neutral | N | 0.485238711 | None | None | N |
| S/D | 0.2811 | likely_benign | 0.3286 | benign | -1.63 | Destabilizing | 0.262 | N | 0.654 | neutral | None | None | None | None | N |
| S/E | 0.3073 | likely_benign | 0.3319 | benign | -1.459 | Destabilizing | 0.262 | N | 0.64 | neutral | None | None | None | None | N |
| S/F | 0.0932 | likely_benign | 0.0858 | benign | -0.387 | Destabilizing | 0.38 | N | 0.662 | neutral | None | None | None | None | N |
| S/G | 0.1077 | likely_benign | 0.1193 | benign | -1.068 | Destabilizing | 0.211 | N | 0.641 | neutral | N | 0.50229392 | None | None | N |
| S/H | 0.1362 | likely_benign | 0.1378 | benign | -1.527 | Destabilizing | 0.935 | D | 0.655 | neutral | None | None | None | None | N |
| S/I | 0.0522 | likely_benign | 0.0575 | benign | 0.259 | Stabilizing | None | N | 0.485 | neutral | N | 0.458348355 | None | None | N |
| S/K | 0.2713 | likely_benign | 0.2967 | benign | -0.775 | Destabilizing | 0.262 | N | 0.641 | neutral | None | None | None | None | N |
| S/L | 0.0637 | likely_benign | 0.0583 | benign | 0.259 | Stabilizing | 0.001 | N | 0.489 | neutral | None | None | None | None | N |
| S/M | 0.099 | likely_benign | 0.0934 | benign | 0.078 | Stabilizing | 0.38 | N | 0.672 | neutral | None | None | None | None | N |
| S/N | 0.0863 | likely_benign | 0.0917 | benign | -1.372 | Destabilizing | 0.211 | N | 0.661 | neutral | N | 0.482457365 | None | None | N |
| S/P | 0.8934 | likely_pathogenic | 0.9032 | pathogenic | -0.022 | Destabilizing | 0.791 | D | 0.675 | neutral | None | None | None | None | N |
| S/Q | 0.2335 | likely_benign | 0.2368 | benign | -1.105 | Destabilizing | 0.791 | D | 0.653 | neutral | None | None | None | None | N |
| S/R | 0.2278 | likely_benign | 0.2413 | benign | -1.095 | Destabilizing | 0.484 | N | 0.675 | neutral | N | 0.450670234 | None | None | N |
| S/T | 0.0598 | likely_benign | 0.0536 | benign | -0.987 | Destabilizing | 0.002 | N | 0.528 | neutral | N | 0.440663884 | None | None | N |
| S/V | 0.0728 | likely_benign | 0.0733 | benign | -0.022 | Destabilizing | 0.012 | N | 0.631 | neutral | None | None | None | None | N |
| S/W | 0.2056 | likely_benign | 0.1892 | benign | -0.743 | Destabilizing | 0.935 | D | 0.737 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1037 | likely_benign | 0.1017 | benign | -0.308 | Destabilizing | 0.555 | D | 0.674 | 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.