Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32174 | 96745;96746;96747 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| N2AB | 30533 | 91822;91823;91824 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| N2A | 29606 | 89041;89042;89043 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| N2B | 23109 | 69550;69551;69552 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| Novex-1 | 23234 | 69925;69926;69927 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| Novex-2 | 23301 | 70126;70127;70128 | chr2:178543453;178543452;178543451 | chr2:179408180;179408179;179408178 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/T | rs749585164  |
-0.958 | 0.468 | N | 0.363 | 0.173 | 0.471456661759 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.79174E-04 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs749585164 |
-0.958 | 0.468 | N | 0.363 | 0.173 | 0.471456661759 | 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 |
| M/T | rs749585164 |
-0.958 | 0.468 | N | 0.363 | 0.173 | 0.471456661759 | gnomAD-4.0.0 | 2.47872E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 7.8017E-04 | None | 0 | 0 | 3.39038E-06 | 1.09782E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.2145 | likely_benign | 0.1962 | benign | -1.805 | Destabilizing | 0.2 | N | 0.245 | neutral | None | None | None | None | N |
| M/C | 0.5718 | likely_pathogenic | 0.5757 | pathogenic | -1.186 | Destabilizing | 0.968 | D | 0.453 | neutral | None | None | None | None | N |
| M/D | 0.7684 | likely_pathogenic | 0.7483 | pathogenic | -0.414 | Destabilizing | 0.582 | D | 0.469 | neutral | None | None | None | None | N |
| M/E | 0.4398 | ambiguous | 0.4105 | ambiguous | -0.316 | Destabilizing | 0.223 | N | 0.331 | neutral | None | None | None | None | N |
| M/F | 0.3756 | ambiguous | 0.3489 | ambiguous | -0.57 | Destabilizing | 0.002 | N | 0.103 | neutral | None | None | None | None | N |
| M/G | 0.4323 | ambiguous | 0.398 | ambiguous | -2.182 | Highly Destabilizing | 0.538 | D | 0.393 | neutral | None | None | None | None | N |
| M/H | 0.4445 | ambiguous | 0.4316 | ambiguous | -1.318 | Destabilizing | 0.002 | N | 0.219 | neutral | None | None | None | None | N |
| M/I | 0.3445 | ambiguous | 0.316 | benign | -0.793 | Destabilizing | 0.178 | N | 0.267 | neutral | N | 0.409716541 | None | None | N |
| M/K | 0.1697 | likely_benign | 0.1721 | benign | -0.549 | Destabilizing | 0.178 | N | 0.335 | neutral | N | 0.396688528 | None | None | N |
| M/L | 0.1042 | likely_benign | 0.0977 | benign | -0.793 | Destabilizing | None | N | 0.068 | neutral | N | 0.382183223 | None | None | N |
| M/N | 0.3761 | ambiguous | 0.3656 | ambiguous | -0.532 | Destabilizing | 0.582 | D | 0.467 | neutral | None | None | None | None | N |
| M/P | 0.4058 | ambiguous | 0.3846 | ambiguous | -1.105 | Destabilizing | 0.896 | D | 0.576 | neutral | None | None | None | None | N |
| M/Q | 0.2094 | likely_benign | 0.205 | benign | -0.474 | Destabilizing | 0.051 | N | 0.1 | neutral | None | None | None | None | N |
| M/R | 0.1885 | likely_benign | 0.1766 | benign | -0.281 | Destabilizing | 0.001 | N | 0.151 | neutral | N | 0.406790879 | None | None | N |
| M/S | 0.247 | likely_benign | 0.2329 | benign | -1.233 | Destabilizing | 0.365 | N | 0.338 | neutral | None | None | None | None | N |
| M/T | 0.1367 | likely_benign | 0.1295 | benign | -1.016 | Destabilizing | 0.468 | N | 0.363 | neutral | N | 0.338661732 | None | None | N |
| M/V | 0.0745 | likely_benign | 0.0697 | benign | -1.105 | Destabilizing | 0.086 | N | 0.165 | neutral | N | 0.381529862 | None | None | N |
| M/W | 0.6247 | likely_pathogenic | 0.6173 | pathogenic | -0.602 | Destabilizing | 0.968 | D | 0.449 | neutral | None | None | None | None | N |
| M/Y | 0.5014 | ambiguous | 0.5049 | ambiguous | -0.61 | Destabilizing | 0.41 | N | 0.417 | 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.