Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17450 | 52573;52574;52575 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| N2AB | 15809 | 47650;47651;47652 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| N2A | 14882 | 44869;44870;44871 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| N2B | 8385 | 25378;25379;25380 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| Novex-1 | 8510 | 25753;25754;25755 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| Novex-2 | 8577 | 25954;25955;25956 | chr2:178608663;178608662;178608661 | chr2:179473390;179473389;179473388 |
| 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 | rs778572247  |
0.026 | 0.001 | N | 0.195 | 0.099 | 0.200317383148 | gnomAD-2.1.1 | 1.22E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.7094E-04 | None | 0 | None | 0 | 0 | 0 |
| R/K | rs778572247 |
0.026 | 0.001 | N | 0.195 | 0.099 | 0.200317383148 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 1.95008E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/K | rs778572247 |
0.026 | 0.001 | N | 0.195 | 0.099 | 0.200317383148 | gnomAD-4.0.0 | 9.92525E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 3.37109E-04 | None | 0 | 0 | 0 | 0 | 1.60282E-05 |
| R/T | None | None | 0.549 | N | 0.484 | 0.093 | 0.276482976112 | gnomAD-4.0.0 | 6.84963E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.0005E-07 | 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 | 0.761 | likely_pathogenic | 0.7518 | pathogenic | -0.138 | Destabilizing | 0.25 | N | 0.426 | neutral | None | None | None | None | I |
| R/C | 0.4285 | ambiguous | 0.4241 | ambiguous | -0.317 | Destabilizing | 0.992 | D | 0.481 | neutral | None | None | None | None | I |
| R/D | 0.9106 | likely_pathogenic | 0.9067 | pathogenic | -0.019 | Destabilizing | 0.617 | D | 0.474 | neutral | None | None | None | None | I |
| R/E | 0.7597 | likely_pathogenic | 0.7319 | pathogenic | 0.07 | Stabilizing | 0.25 | N | 0.388 | neutral | None | None | None | None | I |
| R/F | 0.8609 | likely_pathogenic | 0.8472 | pathogenic | -0.324 | Destabilizing | 0.972 | D | 0.453 | neutral | None | None | None | None | I |
| R/G | 0.7102 | likely_pathogenic | 0.7089 | pathogenic | -0.356 | Destabilizing | 0.549 | D | 0.493 | neutral | N | 0.487729033 | None | None | I |
| R/H | 0.2315 | likely_benign | 0.2233 | benign | -0.94 | Destabilizing | 0.92 | D | 0.331 | neutral | None | None | None | None | I |
| R/I | 0.5122 | ambiguous | 0.4989 | ambiguous | 0.407 | Stabilizing | 0.896 | D | 0.469 | neutral | N | 0.451699236 | None | None | I |
| R/K | 0.1754 | likely_benign | 0.1797 | benign | -0.145 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.373371739 | None | None | I |
| R/L | 0.5026 | ambiguous | 0.4897 | ambiguous | 0.407 | Stabilizing | 0.617 | D | 0.493 | neutral | None | None | None | None | I |
| R/M | 0.609 | likely_pathogenic | 0.5998 | pathogenic | -0.092 | Destabilizing | 0.972 | D | 0.401 | neutral | None | None | None | None | I |
| R/N | 0.8301 | likely_pathogenic | 0.8278 | pathogenic | 0.01 | Stabilizing | 0.617 | D | 0.389 | neutral | None | None | None | None | I |
| R/P | 0.8443 | likely_pathogenic | 0.8065 | pathogenic | 0.246 | Stabilizing | 0.92 | D | 0.475 | neutral | None | None | None | None | I |
| R/Q | 0.2304 | likely_benign | 0.2218 | benign | -0.04 | Destabilizing | 0.447 | N | 0.42 | neutral | None | None | None | None | I |
| R/S | 0.8246 | likely_pathogenic | 0.8165 | pathogenic | -0.394 | Destabilizing | 0.379 | N | 0.477 | neutral | N | 0.431361249 | None | None | I |
| R/T | 0.6301 | likely_pathogenic | 0.6233 | pathogenic | -0.151 | Destabilizing | 0.549 | D | 0.484 | neutral | N | 0.459662572 | None | None | I |
| R/V | 0.6321 | likely_pathogenic | 0.6199 | pathogenic | 0.246 | Stabilizing | 0.85 | D | 0.451 | neutral | None | None | None | None | I |
| R/W | 0.5256 | ambiguous | 0.49 | ambiguous | -0.353 | Destabilizing | 0.992 | D | 0.533 | neutral | None | None | None | None | I |
| R/Y | 0.6846 | likely_pathogenic | 0.6542 | pathogenic | 0.055 | Stabilizing | 0.972 | D | 0.467 | 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.