Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35178 | 105757;105758;105759 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| N2AB | 33537 | 100834;100835;100836 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| N2A | 32610 | 98053;98054;98055 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| N2B | 26113 | 78562;78563;78564 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| Novex-1 | 26238 | 78937;78938;78939 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| Novex-2 | 26305 | 79138;79139;79140 | chr2:178531083;178531082;178531081 | chr2:179395810;179395809;179395808 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs1185377965  |
-0.193 | 0.001 | N | 0.209 | 0.212 | 0.304435445954 | gnomAD-2.1.1 | 4.01E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/I | rs1185377965 |
-0.193 | 0.001 | N | 0.209 | 0.212 | 0.304435445954 | gnomAD-4.0.0 | 3.42068E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.51889E-05 | None | 0 | 0 | 3.59757E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0978 | likely_benign | 0.1094 | benign | -0.46 | Destabilizing | 0.037 | N | 0.265 | neutral | N | 0.510625402 | None | None | N |
| T/C | 0.53 | ambiguous | 0.5845 | pathogenic | -0.134 | Destabilizing | 0.869 | D | 0.381 | neutral | None | None | None | None | N |
| T/D | 0.4124 | ambiguous | 0.4698 | ambiguous | -0.186 | Destabilizing | 0.198 | N | 0.329 | neutral | None | None | None | None | N |
| T/E | 0.3029 | likely_benign | 0.3547 | ambiguous | -0.262 | Destabilizing | 0.11 | N | 0.287 | neutral | None | None | None | None | N |
| T/F | 0.2219 | likely_benign | 0.2516 | benign | -0.927 | Destabilizing | 0.464 | N | 0.459 | neutral | None | None | None | None | N |
| T/G | 0.3301 | likely_benign | 0.3884 | ambiguous | -0.606 | Destabilizing | 0.11 | N | 0.341 | neutral | None | None | None | None | N |
| T/H | 0.2508 | likely_benign | 0.262 | benign | -0.992 | Destabilizing | 0.869 | D | 0.437 | neutral | None | None | None | None | N |
| T/I | 0.1619 | likely_benign | 0.182 | benign | -0.187 | Destabilizing | 0.001 | N | 0.209 | neutral | N | 0.503835502 | None | None | N |
| T/K | 0.203 | likely_benign | 0.213 | benign | -0.407 | Destabilizing | 0.003 | N | 0.269 | neutral | None | None | None | None | N |
| T/L | 0.1249 | likely_benign | 0.1392 | benign | -0.187 | Destabilizing | 0.017 | N | 0.269 | neutral | None | None | None | None | N |
| T/M | 0.1035 | likely_benign | 0.1093 | benign | 0.244 | Stabilizing | 0.464 | N | 0.385 | neutral | None | None | None | None | N |
| T/N | 0.1355 | likely_benign | 0.1483 | benign | -0.168 | Destabilizing | 0.085 | N | 0.305 | neutral | N | 0.506374375 | None | None | N |
| T/P | 0.4809 | ambiguous | 0.5412 | ambiguous | -0.249 | Destabilizing | 0.57 | D | 0.375 | neutral | D | 0.535446488 | None | None | N |
| T/Q | 0.2211 | likely_benign | 0.2386 | benign | -0.489 | Destabilizing | 0.464 | N | 0.382 | neutral | None | None | None | None | N |
| T/R | 0.1523 | likely_benign | 0.164 | benign | -0.074 | Destabilizing | 0.11 | N | 0.354 | neutral | None | None | None | None | N |
| T/S | 0.1179 | likely_benign | 0.1358 | benign | -0.361 | Destabilizing | None | N | 0.085 | neutral | N | 0.439802666 | None | None | N |
| T/V | 0.1561 | likely_benign | 0.1673 | benign | -0.249 | Destabilizing | 0.017 | N | 0.253 | neutral | None | None | None | None | N |
| T/W | 0.5817 | likely_pathogenic | 0.6317 | pathogenic | -0.893 | Destabilizing | 0.953 | D | 0.492 | neutral | None | None | None | None | N |
| T/Y | 0.2999 | likely_benign | 0.3238 | benign | -0.624 | Destabilizing | 0.637 | D | 0.461 | 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.