Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33354 | 100285;100286;100287 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| N2AB | 31713 | 95362;95363;95364 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| N2A | 30786 | 92581;92582;92583 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| N2B | 24289 | 73090;73091;73092 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| Novex-1 | 24414 | 73465;73466;73467 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| Novex-2 | 24481 | 73666;73667;73668 | chr2:178537049;178537048;178537047 | chr2:179401776;179401775;179401774 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs759484221  |
-0.831 | 0.061 | N | 0.158 | 0.122 | 0.461144880706 | gnomAD-2.1.1 | 8.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| V/A | rs759484221 |
-0.831 | 0.061 | N | 0.158 | 0.122 | 0.461144880706 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/A | rs759484221 |
-0.831 | 0.061 | N | 0.158 | 0.122 | 0.461144880706 | gnomAD-4.0.0 | 8.67887E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.18689E-05 | 0 | 0 |
| V/M | rs879221791 |
-0.37 | 0.996 | N | 0.461 | 0.28 | 0.51196500227 | gnomAD-2.1.1 | 3.18E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/M | rs879221791 |
-0.37 | 0.996 | N | 0.461 | 0.28 | 0.51196500227 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs879221791 |
-0.37 | 0.996 | N | 0.461 | 0.28 | 0.51196500227 | gnomAD-4.0.0 | 1.85979E-06 | None | None | None | None | N | None | 2.67058E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.47784E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2242 | likely_benign | 0.2066 | benign | -0.968 | Destabilizing | 0.061 | N | 0.158 | neutral | N | 0.430457172 | None | None | N |
| V/C | 0.7838 | likely_pathogenic | 0.7671 | pathogenic | -0.752 | Destabilizing | 0.999 | D | 0.515 | neutral | None | None | None | None | N |
| V/D | 0.5248 | ambiguous | 0.5624 | ambiguous | -0.486 | Destabilizing | 0.991 | D | 0.601 | neutral | None | None | None | None | N |
| V/E | 0.4401 | ambiguous | 0.5006 | ambiguous | -0.557 | Destabilizing | 0.959 | D | 0.573 | neutral | N | 0.377449407 | None | None | N |
| V/F | 0.3 | likely_benign | 0.3094 | benign | -0.9 | Destabilizing | 0.997 | D | 0.562 | neutral | None | None | None | None | N |
| V/G | 0.2671 | likely_benign | 0.262 | benign | -1.189 | Destabilizing | 0.92 | D | 0.535 | neutral | N | 0.422357764 | None | None | N |
| V/H | 0.7197 | likely_pathogenic | 0.7407 | pathogenic | -0.63 | Destabilizing | 0.999 | D | 0.595 | neutral | None | None | None | None | N |
| V/I | 0.1012 | likely_benign | 0.092 | benign | -0.505 | Destabilizing | 0.927 | D | 0.437 | neutral | None | None | None | None | N |
| V/K | 0.5378 | ambiguous | 0.623 | pathogenic | -0.761 | Destabilizing | 0.969 | D | 0.58 | neutral | None | None | None | None | N |
| V/L | 0.269 | likely_benign | 0.2451 | benign | -0.505 | Destabilizing | 0.826 | D | 0.431 | neutral | N | 0.405292156 | None | None | N |
| V/M | 0.2371 | likely_benign | 0.2117 | benign | -0.427 | Destabilizing | 0.996 | D | 0.461 | neutral | N | 0.435729706 | None | None | N |
| V/N | 0.3508 | ambiguous | 0.3431 | ambiguous | -0.469 | Destabilizing | 0.997 | D | 0.62 | neutral | None | None | None | None | N |
| V/P | 0.3424 | ambiguous | 0.2477 | benign | -0.623 | Destabilizing | 0.02 | N | 0.294 | neutral | None | None | None | None | N |
| V/Q | 0.4274 | ambiguous | 0.4591 | ambiguous | -0.696 | Destabilizing | 0.997 | D | 0.613 | neutral | None | None | None | None | N |
| V/R | 0.4854 | ambiguous | 0.5685 | pathogenic | -0.2 | Destabilizing | 0.991 | D | 0.623 | neutral | None | None | None | None | N |
| V/S | 0.238 | likely_benign | 0.2376 | benign | -0.954 | Destabilizing | 0.884 | D | 0.523 | neutral | None | None | None | None | N |
| V/T | 0.196 | likely_benign | 0.1983 | benign | -0.915 | Destabilizing | 0.939 | D | 0.402 | neutral | None | None | None | None | N |
| V/W | 0.9076 | likely_pathogenic | 0.9081 | pathogenic | -0.97 | Destabilizing | 0.999 | D | 0.624 | neutral | None | None | None | None | N |
| V/Y | 0.7291 | likely_pathogenic | 0.7481 | pathogenic | -0.698 | Destabilizing | 0.997 | D | 0.557 | 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.