Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26960 | 81103;81104;81105 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| N2AB | 25319 | 76180;76181;76182 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| N2A | 24392 | 73399;73400;73401 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| N2B | 17895 | 53908;53909;53910 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| Novex-1 | 18020 | 54283;54284;54285 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| Novex-2 | 18087 | 54484;54485;54486 | chr2:178565254;178565253;178565252 | chr2:179429981;179429980;179429979 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs746547418  |
0.084 | 0.317 | D | 0.555 | 0.22 | 0.321393169273 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| T/I | rs746547418 |
0.084 | 0.317 | D | 0.555 | 0.22 | 0.321393169273 | gnomAD-4.0.0 | 6.84264E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99525E-07 | 0 | 0 |
| T/R | rs746547418 |
None | 0.062 | N | 0.544 | 0.167 | 0.317667799068 | gnomAD-4.0.0 | 6.84264E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15945E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0822 | likely_benign | 0.0802 | benign | -0.552 | Destabilizing | None | N | 0.183 | neutral | N | 0.507622382 | None | None | N |
| T/C | 0.3181 | likely_benign | 0.3187 | benign | -0.268 | Destabilizing | 0.824 | D | 0.528 | neutral | None | None | None | None | N |
| T/D | 0.3447 | ambiguous | 0.3262 | benign | -0.237 | Destabilizing | 0.081 | N | 0.505 | neutral | None | None | None | None | N |
| T/E | 0.1996 | likely_benign | 0.1936 | benign | -0.32 | Destabilizing | 0.001 | N | 0.285 | neutral | None | None | None | None | N |
| T/F | 0.1813 | likely_benign | 0.1744 | benign | -1.032 | Destabilizing | 0.555 | D | 0.605 | neutral | None | None | None | None | N |
| T/G | 0.256 | likely_benign | 0.2414 | benign | -0.684 | Destabilizing | 0.081 | N | 0.537 | neutral | None | None | None | None | N |
| T/H | 0.194 | likely_benign | 0.1909 | benign | -1.047 | Destabilizing | 0.824 | D | 0.589 | neutral | None | None | None | None | N |
| T/I | 0.1021 | likely_benign | 0.1033 | benign | -0.316 | Destabilizing | 0.317 | N | 0.555 | neutral | D | 0.528941804 | None | None | N |
| T/K | 0.1177 | likely_benign | 0.1158 | benign | -0.517 | Destabilizing | None | N | 0.288 | neutral | N | 0.463194027 | None | None | N |
| T/L | 0.0903 | likely_benign | 0.0912 | benign | -0.316 | Destabilizing | 0.081 | N | 0.505 | neutral | None | None | None | None | N |
| T/M | 0.0782 | likely_benign | 0.0769 | benign | 0.093 | Stabilizing | 0.824 | D | 0.53 | neutral | None | None | None | None | N |
| T/N | 0.1154 | likely_benign | 0.1094 | benign | -0.272 | Destabilizing | 0.149 | N | 0.495 | neutral | None | None | None | None | N |
| T/P | 0.3448 | ambiguous | 0.3465 | ambiguous | -0.367 | Destabilizing | 0.317 | N | 0.554 | neutral | N | 0.509432579 | None | None | N |
| T/Q | 0.1541 | likely_benign | 0.1487 | benign | -0.604 | Destabilizing | 0.235 | N | 0.557 | neutral | None | None | None | None | N |
| T/R | 0.1172 | likely_benign | 0.1144 | benign | -0.162 | Destabilizing | 0.062 | N | 0.544 | neutral | N | 0.492076926 | None | None | N |
| T/S | 0.098 | likely_benign | 0.0926 | benign | -0.466 | Destabilizing | 0.005 | N | 0.235 | neutral | N | 0.436548931 | None | None | N |
| T/V | 0.0881 | likely_benign | 0.0887 | benign | -0.367 | Destabilizing | 0.081 | N | 0.433 | neutral | None | None | None | None | N |
| T/W | 0.5396 | ambiguous | 0.5406 | ambiguous | -0.983 | Destabilizing | 0.935 | D | 0.621 | neutral | None | None | None | None | N |
| T/Y | 0.2403 | likely_benign | 0.2337 | benign | -0.729 | Destabilizing | 0.555 | D | 0.605 | 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.