Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21122 | 63589;63590;63591 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| N2AB | 19481 | 58666;58667;58668 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| N2A | 18554 | 55885;55886;55887 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| N2B | 12057 | 36394;36395;36396 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| Novex-1 | 12182 | 36769;36770;36771 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| Novex-2 | 12249 | 36970;36971;36972 | chr2:178588043;178588042;178588041 | chr2:179452770;179452769;179452768 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs377528392  |
-0.183 | 0.852 | N | 0.289 | 0.225 | None | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.93E-06 | 0 |
| A/T | rs377528392 |
-0.183 | 0.852 | N | 0.289 | 0.225 | None | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| A/T | rs377528392 |
-0.183 | 0.852 | N | 0.289 | 0.225 | None | gnomAD-4.0.0 | 2.56477E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.79072E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5487 | ambiguous | 0.4936 | ambiguous | -0.834 | Destabilizing | 0.999 | D | 0.305 | neutral | None | None | None | None | I |
| A/D | 0.3906 | ambiguous | 0.3183 | benign | -0.605 | Destabilizing | 0.939 | D | 0.378 | neutral | None | None | None | None | I |
| A/E | 0.364 | ambiguous | 0.2962 | benign | -0.75 | Destabilizing | 0.92 | D | 0.27 | neutral | N | 0.471053001 | None | None | I |
| A/F | 0.4238 | ambiguous | 0.3652 | ambiguous | -0.976 | Destabilizing | 0.991 | D | 0.363 | neutral | None | None | None | None | I |
| A/G | 0.1535 | likely_benign | 0.1302 | benign | -0.237 | Destabilizing | 0.826 | D | 0.314 | neutral | N | 0.439250014 | None | None | I |
| A/H | 0.5053 | ambiguous | 0.4267 | ambiguous | -0.237 | Destabilizing | 0.046 | N | 0.269 | neutral | None | None | None | None | I |
| A/I | 0.2946 | likely_benign | 0.2436 | benign | -0.476 | Destabilizing | 0.991 | D | 0.316 | neutral | None | None | None | None | I |
| A/K | 0.5236 | ambiguous | 0.4373 | ambiguous | -0.511 | Destabilizing | 0.884 | D | 0.285 | neutral | None | None | None | None | I |
| A/L | 0.2033 | likely_benign | 0.1737 | benign | -0.476 | Destabilizing | 0.969 | D | 0.259 | neutral | None | None | None | None | I |
| A/M | 0.2708 | likely_benign | 0.2398 | benign | -0.62 | Destabilizing | 0.999 | D | 0.266 | neutral | None | None | None | None | I |
| A/N | 0.2813 | likely_benign | 0.2307 | benign | -0.195 | Destabilizing | 0.939 | D | 0.337 | neutral | None | None | None | None | I |
| A/P | 0.1481 | likely_benign | 0.1101 | benign | -0.381 | Destabilizing | 0.988 | D | 0.31 | neutral | N | 0.473935804 | None | None | I |
| A/Q | 0.3651 | ambiguous | 0.2998 | benign | -0.457 | Destabilizing | 0.982 | D | 0.317 | neutral | None | None | None | None | I |
| A/R | 0.489 | ambiguous | 0.4048 | ambiguous | -0.11 | Destabilizing | 0.1 | N | 0.242 | neutral | None | None | None | None | I |
| A/S | 0.1084 | likely_benign | 0.0984 | benign | -0.375 | Destabilizing | 0.31 | N | 0.279 | neutral | N | 0.402518423 | None | None | I |
| A/T | 0.1054 | likely_benign | 0.094 | benign | -0.456 | Destabilizing | 0.852 | D | 0.289 | neutral | N | 0.447080063 | None | None | I |
| A/V | 0.1495 | likely_benign | 0.1261 | benign | -0.381 | Destabilizing | 0.959 | D | 0.334 | neutral | N | 0.445983985 | None | None | I |
| A/W | 0.7766 | likely_pathogenic | 0.7182 | pathogenic | -1.052 | Destabilizing | 0.999 | D | 0.505 | neutral | None | None | None | None | I |
| A/Y | 0.5532 | ambiguous | 0.4691 | ambiguous | -0.756 | Destabilizing | 0.982 | D | 0.375 | 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.