Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16991 | 51196;51197;51198 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| N2AB | 15350 | 46273;46274;46275 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| N2A | 14423 | 43492;43493;43494 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| N2B | 7926 | 24001;24002;24003 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| Novex-1 | 8051 | 24376;24377;24378 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| Novex-2 | 8118 | 24577;24578;24579 | chr2:178611158;178611157;178611156 | chr2:179475885;179475884;179475883 |
| 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 | rs968016218  |
None | 0.977 | N | 0.387 | 0.252 | 0.223847106136 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| D/E | rs968016218 |
None | 0.977 | N | 0.387 | 0.252 | 0.223847106136 | gnomAD-4.0.0 | 7.441E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.01759E-05 | 0 | 0 |
| D/G | rs745796006 |
-0.811 | 0.955 | N | 0.511 | 0.281 | 0.173771789658 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| D/G | rs745796006 |
-0.811 | 0.955 | N | 0.511 | 0.281 | 0.173771789658 | gnomAD-4.0.0 | 1.59338E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86202E-06 | 0 | 0 |
| D/Y | None | None | 1.0 | D | 0.659 | 0.373 | 0.632155945983 | gnomAD-4.0.0 | 1.59338E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.78769E-05 | None | 0 | 0 | 0 | 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 | 0.2669 | likely_benign | 0.2408 | benign | -0.355 | Destabilizing | 0.993 | D | 0.583 | neutral | N | 0.510976615 | None | None | N |
| D/C | 0.6839 | likely_pathogenic | 0.6575 | pathogenic | -0.078 | Destabilizing | 1.0 | D | 0.653 | neutral | None | None | None | None | N |
| D/E | 0.2653 | likely_benign | 0.241 | benign | -0.267 | Destabilizing | 0.977 | D | 0.387 | neutral | N | 0.449050735 | None | None | N |
| D/F | 0.7326 | likely_pathogenic | 0.7254 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.661 | neutral | None | None | None | None | N |
| D/G | 0.1647 | likely_benign | 0.1445 | benign | -0.578 | Destabilizing | 0.955 | D | 0.511 | neutral | N | 0.456180133 | None | None | N |
| D/H | 0.5446 | ambiguous | 0.5156 | ambiguous | 0.022 | Stabilizing | 0.999 | D | 0.629 | neutral | D | 0.599176057 | None | None | N |
| D/I | 0.7245 | likely_pathogenic | 0.6996 | pathogenic | 0.192 | Stabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| D/K | 0.688 | likely_pathogenic | 0.6606 | pathogenic | 0.243 | Stabilizing | 0.995 | D | 0.583 | neutral | None | None | None | None | N |
| D/L | 0.6024 | likely_pathogenic | 0.5611 | ambiguous | 0.192 | Stabilizing | 0.998 | D | 0.667 | neutral | None | None | None | None | N |
| D/M | 0.7949 | likely_pathogenic | 0.7817 | pathogenic | 0.306 | Stabilizing | 1.0 | D | 0.648 | neutral | None | None | None | None | N |
| D/N | 0.1362 | likely_benign | 0.1274 | benign | -0.165 | Destabilizing | 0.117 | N | 0.253 | neutral | N | 0.449394597 | None | None | N |
| D/P | 0.9679 | likely_pathogenic | 0.9543 | pathogenic | 0.032 | Stabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | N |
| D/Q | 0.5783 | likely_pathogenic | 0.54 | ambiguous | -0.103 | Destabilizing | 0.998 | D | 0.597 | neutral | None | None | None | None | N |
| D/R | 0.6927 | likely_pathogenic | 0.658 | pathogenic | 0.457 | Stabilizing | 0.995 | D | 0.627 | neutral | None | None | None | None | N |
| D/S | 0.2216 | likely_benign | 0.2104 | benign | -0.278 | Destabilizing | 0.966 | D | 0.479 | neutral | None | None | None | None | N |
| D/T | 0.5822 | likely_pathogenic | 0.5402 | ambiguous | -0.098 | Destabilizing | 0.995 | D | 0.577 | neutral | None | None | None | None | N |
| D/V | 0.4834 | ambiguous | 0.4524 | ambiguous | 0.032 | Stabilizing | 0.997 | D | 0.673 | neutral | D | 0.581989445 | None | None | N |
| D/W | 0.9285 | likely_pathogenic | 0.9208 | pathogenic | 0.042 | Stabilizing | 1.0 | D | 0.655 | neutral | None | None | None | None | N |
| D/Y | 0.3243 | likely_benign | 0.3132 | benign | 0.108 | Stabilizing | 1.0 | D | 0.659 | neutral | D | 0.660793971 | 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.