Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27718 | 83377;83378;83379 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| N2AB | 26077 | 78454;78455;78456 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| N2A | 25150 | 75673;75674;75675 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| N2B | 18653 | 56182;56183;56184 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| Novex-1 | 18778 | 56557;56558;56559 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| Novex-2 | 18845 | 56758;56759;56760 | chr2:178562980;178562979;178562978 | chr2:179427707;179427706;179427705 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs1198738101  |
-0.034 | None | N | 0.207 | 0.078 | 0.0138822411134 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 0 | 0 |
| D/E | rs1198738101 |
-0.034 | None | N | 0.207 | 0.078 | 0.0138822411134 | gnomAD-4.0.0 | 3.4213E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 5.79683E-05 | 0 |
| D/N | None | None | 0.22 | N | 0.457 | 0.164 | 0.119812018005 | gnomAD-4.0.0 | 1.59152E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85848E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1539 | likely_benign | 0.1527 | benign | 0.089 | Stabilizing | 0.124 | N | 0.427 | neutral | N | 0.511851113 | None | None | I |
| D/C | 0.6191 | likely_pathogenic | 0.6303 | pathogenic | -0.01 | Destabilizing | 0.968 | D | 0.538 | neutral | None | None | None | None | I |
| D/E | 0.0858 | likely_benign | 0.0793 | benign | -0.306 | Destabilizing | None | N | 0.207 | neutral | N | 0.420671748 | None | None | I |
| D/F | 0.7037 | likely_pathogenic | 0.7027 | pathogenic | -0.116 | Destabilizing | 0.89 | D | 0.481 | neutral | None | None | None | None | I |
| D/G | 0.1447 | likely_benign | 0.1367 | benign | 0.004 | Stabilizing | 0.22 | N | 0.406 | neutral | N | 0.47034842 | None | None | I |
| D/H | 0.2882 | likely_benign | 0.2883 | benign | 0.452 | Stabilizing | 0.667 | D | 0.426 | neutral | N | 0.471696455 | None | None | I |
| D/I | 0.4231 | ambiguous | 0.4259 | ambiguous | 0.239 | Stabilizing | 0.726 | D | 0.48 | neutral | None | None | None | None | I |
| D/K | 0.2678 | likely_benign | 0.2592 | benign | 0.473 | Stabilizing | 0.001 | N | 0.261 | neutral | None | None | None | None | I |
| D/L | 0.4025 | ambiguous | 0.3853 | ambiguous | 0.239 | Stabilizing | 0.567 | D | 0.439 | neutral | None | None | None | None | I |
| D/M | 0.5796 | likely_pathogenic | 0.5809 | pathogenic | 0.092 | Stabilizing | 0.968 | D | 0.485 | neutral | None | None | None | None | I |
| D/N | 0.1032 | likely_benign | 0.1055 | benign | 0.371 | Stabilizing | 0.22 | N | 0.457 | neutral | N | 0.485184587 | None | None | I |
| D/P | 0.3394 | likely_benign | 0.3233 | benign | 0.207 | Stabilizing | 0.726 | D | 0.409 | neutral | None | None | None | None | I |
| D/Q | 0.2369 | likely_benign | 0.2322 | benign | 0.344 | Stabilizing | 0.157 | N | 0.401 | neutral | None | None | None | None | I |
| D/R | 0.3641 | ambiguous | 0.3655 | ambiguous | 0.625 | Stabilizing | 0.396 | N | 0.431 | neutral | None | None | None | None | I |
| D/S | 0.1086 | likely_benign | 0.1049 | benign | 0.256 | Stabilizing | 0.157 | N | 0.411 | neutral | None | None | None | None | I |
| D/T | 0.2043 | likely_benign | 0.2031 | benign | 0.324 | Stabilizing | 0.272 | N | 0.416 | neutral | None | None | None | None | I |
| D/V | 0.251 | likely_benign | 0.2436 | benign | 0.207 | Stabilizing | 0.497 | N | 0.438 | neutral | N | 0.462986723 | None | None | I |
| D/W | 0.8788 | likely_pathogenic | 0.8838 | pathogenic | -0.122 | Destabilizing | 0.968 | D | 0.579 | neutral | None | None | None | None | I |
| D/Y | 0.3611 | ambiguous | 0.3655 | ambiguous | 0.1 | Stabilizing | 0.859 | D | 0.481 | neutral | N | 0.46511309 | 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.