Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31002 | 93229;93230;93231 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| N2AB | 29361 | 88306;88307;88308 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| N2A | 28434 | 85525;85526;85527 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| N2B | 21937 | 66034;66035;66036 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| Novex-1 | 22062 | 66409;66410;66411 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| Novex-2 | 22129 | 66610;66611;66612 | chr2:178548622;178548621;178548620 | chr2:179413349;179413348;179413347 |
| 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/I | rs180975448  |
-0.154 | 0.949 | N | 0.627 | 0.298 | None | gnomAD-2.1.1 | 6.25348E-04 | None | None | None | None | I | None | 1.23987E-04 | 5.65E-05 | None | 1.93536E-04 | 0 | None | 0 | None | 5.59463E-04 | 1.18274E-03 | 4.20994E-04 |
| S/I | rs180975448 |
-0.154 | 0.949 | N | 0.627 | 0.298 | None | gnomAD-3.1.2 | 4.79796E-04 | None | None | None | None | I | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 2.82912E-04 | 0 | 9.7016E-04 | 0 | 4.78011E-04 |
| S/I | rs180975448 |
-0.154 | 0.949 | N | 0.627 | 0.298 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| S/I | rs180975448 |
-0.154 | 0.949 | N | 0.627 | 0.298 | None | gnomAD-4.0.0 | 8.25343E-04 | None | None | None | None | I | None | 6.66382E-05 | 6.66689E-05 | None | 1.35126E-04 | 0 | None | 4.21835E-04 | 0 | 1.0688E-03 | 0 | 4.96159E-04 |
| S/R | rs758706423 |
0.076 | 0.901 | N | 0.565 | 0.409 | 0.345405024496 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0843 | likely_benign | 0.0836 | benign | -0.247 | Destabilizing | 0.587 | D | 0.551 | neutral | None | None | None | None | I |
| S/C | 0.0773 | likely_benign | 0.0762 | benign | -0.224 | Destabilizing | 0.995 | D | 0.605 | neutral | N | 0.519591602 | None | None | I |
| S/D | 0.6445 | likely_pathogenic | 0.6381 | pathogenic | -0.099 | Destabilizing | 0.633 | D | 0.501 | neutral | None | None | None | None | I |
| S/E | 0.7255 | likely_pathogenic | 0.7143 | pathogenic | -0.216 | Destabilizing | 0.775 | D | 0.511 | neutral | None | None | None | None | I |
| S/F | 0.3054 | likely_benign | 0.3123 | benign | -1.017 | Destabilizing | 0.987 | D | 0.637 | neutral | None | None | None | None | I |
| S/G | 0.1221 | likely_benign | 0.1063 | benign | -0.28 | Destabilizing | 0.008 | N | 0.318 | neutral | D | 0.531942036 | None | None | I |
| S/H | 0.4437 | ambiguous | 0.4314 | ambiguous | -0.728 | Destabilizing | 0.979 | D | 0.575 | neutral | None | None | None | None | I |
| S/I | 0.1501 | likely_benign | 0.1582 | benign | -0.287 | Destabilizing | 0.949 | D | 0.627 | neutral | N | 0.480590496 | None | None | I |
| S/K | 0.8172 | likely_pathogenic | 0.8168 | pathogenic | -0.366 | Destabilizing | 0.633 | D | 0.508 | neutral | None | None | None | None | I |
| S/L | 0.1284 | likely_benign | 0.1393 | benign | -0.287 | Destabilizing | 0.923 | D | 0.539 | neutral | None | None | None | None | I |
| S/M | 0.2351 | likely_benign | 0.2325 | benign | -0.05 | Destabilizing | 0.996 | D | 0.601 | neutral | None | None | None | None | I |
| S/N | 0.2174 | likely_benign | 0.2233 | benign | -0.065 | Destabilizing | 0.008 | N | 0.469 | neutral | N | 0.493559793 | None | None | I |
| S/P | 0.8249 | likely_pathogenic | 0.8133 | pathogenic | -0.251 | Destabilizing | 0.961 | D | 0.563 | neutral | None | None | None | None | I |
| S/Q | 0.6398 | likely_pathogenic | 0.6191 | pathogenic | -0.338 | Destabilizing | 0.923 | D | 0.537 | neutral | None | None | None | None | I |
| S/R | 0.7209 | likely_pathogenic | 0.7123 | pathogenic | -0.137 | Destabilizing | 0.901 | D | 0.565 | neutral | N | 0.519244885 | None | None | I |
| S/T | 0.1165 | likely_benign | 0.116 | benign | -0.176 | Destabilizing | 0.722 | D | 0.526 | neutral | N | 0.484843409 | None | None | I |
| S/V | 0.1723 | likely_benign | 0.1707 | benign | -0.251 | Destabilizing | 0.961 | D | 0.577 | neutral | None | None | None | None | I |
| S/W | 0.5212 | ambiguous | 0.5134 | ambiguous | -1.082 | Destabilizing | 0.996 | D | 0.689 | prob.neutral | None | None | None | None | I |
| S/Y | 0.2925 | likely_benign | 0.2854 | benign | -0.777 | Destabilizing | 0.987 | D | 0.639 | neutral | 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.