Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21155 | 63688;63689;63690 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| N2AB | 19514 | 58765;58766;58767 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| N2A | 18587 | 55984;55985;55986 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| N2B | 12090 | 36493;36494;36495 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| Novex-1 | 12215 | 36868;36869;36870 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| Novex-2 | 12282 | 37069;37070;37071 | chr2:178587944;178587943;178587942 | chr2:179452671;179452670;179452669 |
| 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/C | rs374727686  |
-0.147 | 1.0 | N | 0.775 | 0.393 | None | gnomAD-2.1.1 | 2.95E-05 | None | None | None | None | I | None | 0 | 8.7E-05 | None | 0 | 5.34E-05 | None | 6.69E-05 | None | 0 | 1.62E-05 | 0 |
| R/C | rs374727686 |
-0.147 | 1.0 | N | 0.775 | 0.393 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 4.14422E-04 | 0 |
| R/C | rs374727686 |
-0.147 | 1.0 | N | 0.775 | 0.393 | None | gnomAD-4.0.0 | 3.54365E-05 | None | None | None | None | I | None | 0 | 6.73514E-05 | None | 0 | 0 | None | 0 | 0 | 3.22829E-05 | 1.32582E-04 | 4.8185E-05 |
| R/H | rs373169150 |
-1.036 | 1.0 | N | 0.765 | 0.352 | None | gnomAD-2.1.1 | 4.8E-05 | None | None | None | None | I | None | 8.53E-05 | 0 | None | 0 | 1.07043E-04 | None | 3.35E-05 | None | 0 | 6.51E-05 | 0 |
| R/H | rs373169150 |
-1.036 | 1.0 | N | 0.765 | 0.352 | None | gnomAD-3.1.2 | 5.26E-05 | None | None | None | None | I | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 1.03005E-04 | 0 | 0 |
| R/H | rs373169150 |
-1.036 | 1.0 | N | 0.765 | 0.352 | None | gnomAD-4.0.0 | 6.03448E-05 | None | None | None | None | I | None | 2.67401E-05 | 5.05834E-05 | None | 0 | 1.35068E-04 | None | 1.56986E-05 | 1.6518E-04 | 6.63112E-05 | 2.21268E-05 | 6.42921E-05 |
| R/L | None | None | 1.0 | N | 0.682 | 0.501 | 0.491863012465 | gnomAD-4.0.0 | 6.87085E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.16885E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.3308 | likely_benign | 0.3316 | benign | 0.013 | Stabilizing | 0.999 | D | 0.63 | neutral | None | None | None | None | I |
| R/C | 0.1825 | likely_benign | 0.1701 | benign | -0.174 | Destabilizing | 1.0 | D | 0.775 | deleterious | N | 0.480371687 | None | None | I |
| R/D | 0.5254 | ambiguous | 0.522 | ambiguous | -0.104 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| R/E | 0.2688 | likely_benign | 0.2581 | benign | -0.045 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | I |
| R/F | 0.4534 | ambiguous | 0.4368 | ambiguous | -0.241 | Destabilizing | 1.0 | D | 0.738 | prob.delet. | None | None | None | None | I |
| R/G | 0.2696 | likely_benign | 0.2709 | benign | -0.169 | Destabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.465720017 | None | None | I |
| R/H | 0.1036 | likely_benign | 0.0973 | benign | -0.673 | Destabilizing | 1.0 | D | 0.765 | deleterious | N | 0.517076079 | None | None | I |
| R/I | 0.2497 | likely_benign | 0.2289 | benign | 0.453 | Stabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| R/K | 0.0975 | likely_benign | 0.0986 | benign | -0.082 | Destabilizing | 0.998 | D | 0.555 | neutral | None | None | None | None | I |
| R/L | 0.1948 | likely_benign | 0.1864 | benign | 0.453 | Stabilizing | 1.0 | D | 0.682 | prob.neutral | N | 0.450179084 | None | None | I |
| R/M | 0.2616 | likely_benign | 0.25 | benign | 0.023 | Stabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/N | 0.4528 | ambiguous | 0.4524 | ambiguous | 0.111 | Stabilizing | 1.0 | D | 0.777 | deleterious | None | None | None | None | I |
| R/P | 0.3345 | likely_benign | 0.3199 | benign | 0.327 | Stabilizing | 1.0 | D | 0.757 | deleterious | N | 0.427856797 | None | None | I |
| R/Q | 0.0954 | likely_benign | 0.094 | benign | 0.026 | Stabilizing | 1.0 | D | 0.774 | deleterious | None | None | None | None | I |
| R/S | 0.4135 | ambiguous | 0.4121 | ambiguous | -0.202 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | N | 0.494103219 | None | None | I |
| R/T | 0.2489 | likely_benign | 0.2417 | benign | -0.015 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/V | 0.305 | likely_benign | 0.2878 | benign | 0.327 | Stabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | I |
| R/W | 0.1841 | likely_benign | 0.1761 | benign | -0.327 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | I |
| R/Y | 0.3307 | likely_benign | 0.3104 | benign | 0.089 | Stabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | I |
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.