Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 34435 | 103528;103529;103530 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| N2AB | 32794 | 98605;98606;98607 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| N2A | 31867 | 95824;95825;95826 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| N2B | 25370 | 76333;76334;76335 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| Novex-1 | 25495 | 76708;76709;76710 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| Novex-2 | 25562 | 76909;76910;76911 | chr2:178533312;178533311;178533310 | chr2:179398039;179398038;179398037 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/K | rs1309913813  |
-1.639 | 0.219 | N | 0.269 | 0.152 | 0.235038932564 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.87E-06 | 0 |
| R/K | rs1309913813 |
-1.639 | 0.219 | N | 0.269 | 0.152 | 0.235038932564 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85768E-06 | 0 | 0 |
| R/T | None | None | 0.99 | N | 0.455 | 0.283 | 0.574843327095 | gnomAD-4.0.0 | 1.59105E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.4108E-04 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.8836 | likely_pathogenic | 0.903 | pathogenic | -1.362 | Destabilizing | 0.985 | D | 0.473 | neutral | None | None | None | None | N |
| R/C | 0.4963 | ambiguous | 0.524 | ambiguous | -1.569 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| R/D | 0.9878 | likely_pathogenic | 0.9883 | pathogenic | -0.905 | Destabilizing | 0.998 | D | 0.587 | neutral | None | None | None | None | N |
| R/E | 0.8772 | likely_pathogenic | 0.8869 | pathogenic | -0.832 | Destabilizing | 0.985 | D | 0.381 | neutral | None | None | None | None | N |
| R/F | 0.9508 | likely_pathogenic | 0.9483 | pathogenic | -1.592 | Destabilizing | 0.998 | D | 0.682 | prob.neutral | None | None | None | None | N |
| R/G | 0.8783 | likely_pathogenic | 0.8921 | pathogenic | -1.589 | Destabilizing | 0.99 | D | 0.517 | neutral | N | 0.503640714 | None | None | N |
| R/H | 0.3062 | likely_benign | 0.3117 | benign | -1.485 | Destabilizing | 0.999 | D | 0.475 | neutral | None | None | None | None | N |
| R/I | 0.7536 | likely_pathogenic | 0.7614 | pathogenic | -0.758 | Destabilizing | 0.989 | D | 0.647 | neutral | N | 0.474184599 | None | None | N |
| R/K | 0.2411 | likely_benign | 0.226 | benign | -1.537 | Destabilizing | 0.219 | N | 0.269 | neutral | N | 0.425139858 | None | None | N |
| R/L | 0.6702 | likely_pathogenic | 0.6877 | pathogenic | -0.758 | Destabilizing | 0.971 | D | 0.543 | neutral | None | None | None | None | N |
| R/M | 0.7622 | likely_pathogenic | 0.7705 | pathogenic | -0.782 | Destabilizing | 0.931 | D | 0.472 | neutral | None | None | None | None | N |
| R/N | 0.9585 | likely_pathogenic | 0.9618 | pathogenic | -0.969 | Destabilizing | 0.998 | D | 0.425 | neutral | None | None | None | None | N |
| R/P | 0.9986 | likely_pathogenic | 0.9982 | pathogenic | -0.943 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| R/Q | 0.2654 | likely_benign | 0.2847 | benign | -1.361 | Destabilizing | 0.985 | D | 0.442 | neutral | None | None | None | None | N |
| R/S | 0.9111 | likely_pathogenic | 0.924 | pathogenic | -1.779 | Destabilizing | 0.98 | D | 0.426 | neutral | N | 0.424139781 | None | None | N |
| R/T | 0.7125 | likely_pathogenic | 0.7463 | pathogenic | -1.563 | Destabilizing | 0.99 | D | 0.455 | neutral | N | 0.363992612 | None | None | N |
| R/V | 0.7919 | likely_pathogenic | 0.8021 | pathogenic | -0.943 | Destabilizing | 0.971 | D | 0.566 | neutral | None | None | None | None | N |
| R/W | 0.6893 | likely_pathogenic | 0.6858 | pathogenic | -1.213 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| R/Y | 0.893 | likely_pathogenic | 0.8962 | pathogenic | -0.88 | Destabilizing | 0.999 | D | 0.655 | 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.