Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 35310 | 106153;106154;106155 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| N2AB | 33669 | 101230;101231;101232 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| N2A | 32742 | 98449;98450;98451 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| N2B | 26245 | 78958;78959;78960 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| Novex-1 | 26370 | 79333;79334;79335 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| Novex-2 | 26437 | 79534;79535;79536 | chr2:178530687;178530686;178530685 | chr2:179395414;179395413;179395412 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/G | None | None | 0.089 | N | 0.353 | 0.111 | 0.144782658237 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 6.07533E-05 | 0 |
| S/N | rs1553484229  |
None | 0.001 | N | 0.118 | 0.036 | 0.0716867268079 | gnomAD-4.0.0 | 1.59091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85757E-06 | 0 | 0 |
| S/T | rs1553484229 |
None | 0.001 | N | 0.123 | 0.057 | 0.0762999501168 | gnomAD-4.0.0 | 1.59091E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85757E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0866 | likely_benign | 0.0933 | benign | -0.155 | Destabilizing | 0.054 | N | 0.284 | neutral | None | None | None | None | N |
| S/C | 0.1525 | likely_benign | 0.159 | benign | -0.52 | Destabilizing | 0.975 | D | 0.509 | neutral | N | 0.451638465 | None | None | N |
| S/D | 0.236 | likely_benign | 0.2551 | benign | -0.007 | Destabilizing | 0.001 | N | 0.123 | neutral | None | None | None | None | N |
| S/E | 0.3858 | ambiguous | 0.4296 | ambiguous | -0.113 | Destabilizing | 0.115 | N | 0.341 | neutral | None | None | None | None | N |
| S/F | 0.2714 | likely_benign | 0.3059 | benign | -0.917 | Destabilizing | 0.817 | D | 0.634 | neutral | None | None | None | None | N |
| S/G | 0.0793 | likely_benign | 0.0882 | benign | -0.181 | Destabilizing | 0.089 | N | 0.353 | neutral | N | 0.441661285 | None | None | N |
| S/H | 0.3038 | likely_benign | 0.3449 | ambiguous | -0.452 | Destabilizing | 0.817 | D | 0.529 | neutral | None | None | None | None | N |
| S/I | 0.1946 | likely_benign | 0.2238 | benign | -0.216 | Destabilizing | 0.454 | N | 0.597 | neutral | N | 0.480170264 | None | None | N |
| S/K | 0.5374 | ambiguous | 0.6047 | pathogenic | -0.418 | Destabilizing | 0.206 | N | 0.285 | neutral | None | None | None | None | N |
| S/L | 0.1382 | likely_benign | 0.1472 | benign | -0.216 | Destabilizing | 0.239 | N | 0.567 | neutral | None | None | None | None | N |
| S/M | 0.2498 | likely_benign | 0.2822 | benign | -0.268 | Destabilizing | 0.817 | D | 0.52 | neutral | None | None | None | None | N |
| S/N | 0.105 | likely_benign | 0.1174 | benign | -0.269 | Destabilizing | 0.001 | N | 0.118 | neutral | N | 0.434648618 | None | None | N |
| S/P | 0.1276 | likely_benign | 0.1509 | benign | -0.173 | Destabilizing | 0.56 | D | 0.489 | neutral | None | None | None | None | N |
| S/Q | 0.4354 | ambiguous | 0.5117 | ambiguous | -0.459 | Destabilizing | 0.386 | N | 0.397 | neutral | None | None | None | None | N |
| S/R | 0.4273 | ambiguous | 0.5036 | ambiguous | -0.18 | Destabilizing | 0.322 | N | 0.491 | neutral | N | 0.486808235 | None | None | N |
| S/T | 0.0799 | likely_benign | 0.0856 | benign | -0.371 | Destabilizing | 0.001 | N | 0.123 | neutral | N | 0.468857192 | None | None | N |
| S/V | 0.1951 | likely_benign | 0.2238 | benign | -0.173 | Destabilizing | 0.239 | N | 0.568 | neutral | None | None | None | None | N |
| S/W | 0.409 | ambiguous | 0.4424 | ambiguous | -1.021 | Destabilizing | 0.981 | D | 0.648 | neutral | None | None | None | None | N |
| S/Y | 0.2547 | likely_benign | 0.2696 | benign | -0.698 | Destabilizing | 0.932 | D | 0.626 | 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.