Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22367 | 67324;67325;67326 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| N2AB | 20726 | 62401;62402;62403 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| N2A | 19799 | 59620;59621;59622 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| N2B | 13302 | 40129;40130;40131 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| Novex-1 | 13427 | 40504;40505;40506 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| Novex-2 | 13494 | 40705;40706;40707 | chr2:178580188;178580187;178580186 | chr2:179444915;179444914;179444913 |
| 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/P | rs72646873  |
-0.662 | 0.949 | N | 0.457 | 0.356 | None | gnomAD-2.1.1 | 1.70763E-03 | None | None | None | None | N | None | 5.37368E-04 | 9.07132E-04 | None | 3.19767E-03 | 0 | None | 2.42099E-03 | None | 1.19971E-04 | 2.4619E-03 | 1.12771E-03 |
| S/P | rs72646873 |
-0.662 | 0.949 | N | 0.457 | 0.356 | None | gnomAD-3.1.2 | 1.88022E-03 | None | None | None | None | N | None | 7.47817E-04 | 2.88373E-03 | 0 | 4.03226E-03 | 0 | None | 1.88395E-04 | 0 | 2.63243E-03 | 2.48242E-03 | 1.91205E-03 |
| S/P | rs72646873 |
-0.662 | 0.949 | N | 0.457 | 0.356 | None | 1000 genomes | 1.19808E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 1E-03 | None | None | None | 4.1E-03 | None |
| S/P | rs72646873 |
-0.662 | 0.949 | N | 0.457 | 0.356 | None | gnomAD-4.0.0 | 3.29725E-03 | None | None | None | None | N | None | 6.53229E-04 | 1.48412E-03 | None | 3.44781E-03 | 0 | None | 1.56299E-04 | 6.61376E-04 | 3.96279E-03 | 2.13084E-03 | 3.15543E-03 |
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 | 0.1335 | likely_benign | 0.1145 | benign | -0.617 | Destabilizing | 0.349 | N | 0.457 | neutral | D | 0.526159709 | None | None | N |
| S/C | 0.146 | likely_benign | 0.1133 | benign | -0.46 | Destabilizing | 0.018 | N | 0.461 | neutral | N | 0.497238628 | None | None | N |
| S/D | 0.5902 | likely_pathogenic | 0.4196 | ambiguous | -0.579 | Destabilizing | 0.775 | D | 0.423 | neutral | None | None | None | None | N |
| S/E | 0.7352 | likely_pathogenic | 0.584 | pathogenic | -0.639 | Destabilizing | 0.775 | D | 0.425 | neutral | None | None | None | None | N |
| S/F | 0.4437 | ambiguous | 0.3339 | benign | -1.097 | Destabilizing | 0.949 | D | 0.55 | neutral | N | 0.487692748 | None | None | N |
| S/G | 0.108 | likely_benign | 0.0924 | benign | -0.778 | Destabilizing | 0.775 | D | 0.421 | neutral | None | None | None | None | N |
| S/H | 0.5075 | ambiguous | 0.38 | ambiguous | -1.355 | Destabilizing | 0.996 | D | 0.467 | neutral | None | None | None | None | N |
| S/I | 0.4686 | ambiguous | 0.3508 | ambiguous | -0.308 | Destabilizing | 0.923 | D | 0.521 | neutral | None | None | None | None | N |
| S/K | 0.8095 | likely_pathogenic | 0.6817 | pathogenic | -0.712 | Destabilizing | 0.775 | D | 0.427 | neutral | None | None | None | None | N |
| S/L | 0.172 | likely_benign | 0.1426 | benign | -0.308 | Destabilizing | 0.633 | D | 0.479 | neutral | None | None | None | None | N |
| S/M | 0.3159 | likely_benign | 0.2582 | benign | 0.18 | Stabilizing | 0.996 | D | 0.471 | neutral | None | None | None | None | N |
| S/N | 0.2175 | likely_benign | 0.1523 | benign | -0.59 | Destabilizing | 0.775 | D | 0.467 | neutral | None | None | None | None | N |
| S/P | 0.9359 | likely_pathogenic | 0.8787 | pathogenic | -0.381 | Destabilizing | 0.949 | D | 0.457 | neutral | N | 0.505543514 | None | None | N |
| S/Q | 0.6186 | likely_pathogenic | 0.495 | ambiguous | -0.921 | Destabilizing | 0.961 | D | 0.431 | neutral | None | None | None | None | N |
| S/R | 0.7401 | likely_pathogenic | 0.5986 | pathogenic | -0.45 | Destabilizing | 0.923 | D | 0.454 | neutral | None | None | None | None | N |
| S/T | 0.0745 | likely_benign | 0.0714 | benign | -0.627 | Destabilizing | 0.003 | N | 0.137 | neutral | N | 0.406540163 | None | None | N |
| S/V | 0.4141 | ambiguous | 0.3105 | benign | -0.381 | Destabilizing | 0.633 | D | 0.491 | neutral | None | None | None | None | N |
| S/W | 0.6282 | likely_pathogenic | 0.4969 | ambiguous | -1.054 | Destabilizing | 0.996 | D | 0.641 | neutral | None | None | None | None | N |
| S/Y | 0.3918 | ambiguous | 0.2976 | benign | -0.788 | Destabilizing | 0.983 | D | 0.551 | neutral | N | 0.48667879000000003 | 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.