Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15169 | 45730;45731;45732 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| N2AB | 13528 | 40807;40808;40809 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| N2A | 12601 | 38026;38027;38028 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| N2B | 6104 | 18535;18536;18537 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| Novex-1 | 6229 | 18910;18911;18912 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| Novex-2 | 6296 | 19111;19112;19113 | chr2:178621213;178621212;178621211 | chr2:179485940;179485939;179485938 |
| 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/T | rs759247684  |
-0.546 | 0.007 | N | 0.231 | 0.074 | 0.226586394389 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| A/T | rs759247684 |
-0.546 | 0.007 | N | 0.231 | 0.074 | 0.226586394389 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs759247684 |
-0.546 | 0.007 | N | 0.231 | 0.074 | 0.226586394389 | gnomAD-4.0.0 | 1.17849E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61137E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5009 | ambiguous | 0.3889 | ambiguous | -0.812 | Destabilizing | 0.984 | D | 0.565 | neutral | None | None | None | None | N |
| A/D | 0.3117 | likely_benign | 0.2542 | benign | -0.54 | Destabilizing | 0.684 | D | 0.619 | neutral | N | 0.45705072 | None | None | N |
| A/E | 0.2848 | likely_benign | 0.2332 | benign | -0.686 | Destabilizing | 0.742 | D | 0.548 | neutral | None | None | None | None | N |
| A/F | 0.337 | likely_benign | 0.2994 | benign | -0.923 | Destabilizing | 0.953 | D | 0.66 | neutral | None | None | None | None | N |
| A/G | 0.1671 | likely_benign | 0.1524 | benign | -0.453 | Destabilizing | 0.309 | N | 0.489 | neutral | N | 0.463874147 | None | None | N |
| A/H | 0.5106 | ambiguous | 0.4354 | ambiguous | -0.495 | Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | N |
| A/I | 0.2305 | likely_benign | 0.2065 | benign | -0.371 | Destabilizing | 0.59 | D | 0.549 | neutral | None | None | None | None | N |
| A/K | 0.5462 | ambiguous | 0.4603 | ambiguous | -0.757 | Destabilizing | 0.742 | D | 0.545 | neutral | None | None | None | None | N |
| A/L | 0.1894 | likely_benign | 0.1711 | benign | -0.371 | Destabilizing | 0.373 | N | 0.515 | neutral | None | None | None | None | N |
| A/M | 0.2457 | likely_benign | 0.2172 | benign | -0.387 | Destabilizing | 0.953 | D | 0.565 | neutral | None | None | None | None | N |
| A/N | 0.2669 | likely_benign | 0.2352 | benign | -0.429 | Destabilizing | 0.742 | D | 0.625 | neutral | None | None | None | None | N |
| A/P | 0.3415 | ambiguous | 0.2989 | benign | -0.338 | Destabilizing | 0.939 | D | 0.549 | neutral | N | 0.462478029 | None | None | N |
| A/Q | 0.3962 | ambiguous | 0.3386 | benign | -0.71 | Destabilizing | 0.953 | D | 0.56 | neutral | None | None | None | None | N |
| A/R | 0.4795 | ambiguous | 0.4081 | ambiguous | -0.276 | Destabilizing | 0.91 | D | 0.563 | neutral | None | None | None | None | N |
| A/S | 0.0873 | likely_benign | 0.0817 | benign | -0.649 | Destabilizing | 0.004 | N | 0.233 | neutral | N | 0.351136939 | None | None | N |
| A/T | 0.0793 | likely_benign | 0.0779 | benign | -0.713 | Destabilizing | 0.007 | N | 0.231 | neutral | N | 0.469389385 | None | None | N |
| A/V | 0.128 | likely_benign | 0.1178 | benign | -0.338 | Destabilizing | 0.028 | N | 0.248 | neutral | N | 0.450424664 | None | None | N |
| A/W | 0.7654 | likely_pathogenic | 0.6782 | pathogenic | -1.07 | Destabilizing | 0.996 | D | 0.668 | neutral | None | None | None | None | N |
| A/Y | 0.5147 | ambiguous | 0.4462 | ambiguous | -0.725 | Destabilizing | 0.984 | D | 0.659 | 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.