Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6510 | 19753;19754;19755 | chr2:178728296;178728295;178728294 | chr2:179593023;179593022;179593021 |
| N2AB | 6193 | 18802;18803;18804 | chr2:178728296;178728295;178728294 | chr2:179593023;179593022;179593021 |
| N2A | 5266 | 16021;16022;16023 | chr2:178728296;178728295;178728294 | chr2:179593023;179593022;179593021 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs775784361  |
-1.956 | 0.939 | N | 0.643 | 0.413 | 0.683080398064 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 4.66E-05 | 0 | 0 |
| I/T | rs775784361 |
-1.956 | 0.939 | N | 0.643 | 0.413 | 0.683080398064 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.78011E-04 |
| I/T | rs775784361 |
-1.956 | 0.939 | N | 0.643 | 0.413 | 0.683080398064 | gnomAD-4.0.0 | 2.5641E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.57164E-05 | 0 | 0 | 0 | 2.8477E-05 |
| I/V | rs761041978 |
-1.501 | 0.02 | N | 0.198 | 0.138 | None | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.14E-05 | 0 |
| I/V | rs761041978 |
-1.501 | 0.02 | N | 0.198 | 0.138 | None | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 0 | 0 |
| I/V | rs761041978 |
-1.501 | 0.02 | N | 0.198 | 0.138 | None | gnomAD-4.0.0 | 3.84345E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.56455E-05 | 0 | 5.00198E-05 | 0 | 3.2042E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.727 | likely_pathogenic | 0.6959 | pathogenic | -2.174 | Highly Destabilizing | 0.91 | D | 0.493 | neutral | None | None | None | None | I |
| I/C | 0.9132 | likely_pathogenic | 0.9013 | pathogenic | -1.672 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | I |
| I/D | 0.9712 | likely_pathogenic | 0.968 | pathogenic | -2.082 | Highly Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | I |
| I/E | 0.9471 | likely_pathogenic | 0.94 | pathogenic | -2.026 | Highly Destabilizing | 0.993 | D | 0.764 | deleterious | None | None | None | None | I |
| I/F | 0.2377 | likely_benign | 0.2226 | benign | -1.569 | Destabilizing | 0.991 | D | 0.639 | neutral | N | 0.489086598 | None | None | I |
| I/G | 0.9424 | likely_pathogenic | 0.9298 | pathogenic | -2.559 | Highly Destabilizing | 0.993 | D | 0.757 | deleterious | None | None | None | None | I |
| I/H | 0.9084 | likely_pathogenic | 0.9039 | pathogenic | -1.852 | Destabilizing | 0.999 | D | 0.719 | prob.delet. | None | None | None | None | I |
| I/K | 0.8787 | likely_pathogenic | 0.8613 | pathogenic | -1.549 | Destabilizing | 0.993 | D | 0.762 | deleterious | None | None | None | None | I |
| I/L | 0.1255 | likely_benign | 0.1263 | benign | -1.143 | Destabilizing | 0.58 | D | 0.411 | neutral | N | 0.489476551 | None | None | I |
| I/M | 0.1494 | likely_benign | 0.1398 | benign | -1.051 | Destabilizing | 0.991 | D | 0.611 | neutral | N | 0.488099093 | None | None | I |
| I/N | 0.8008 | likely_pathogenic | 0.7972 | pathogenic | -1.491 | Destabilizing | 0.997 | D | 0.764 | deleterious | D | 0.522839572 | None | None | I |
| I/P | 0.863 | likely_pathogenic | 0.8511 | pathogenic | -1.46 | Destabilizing | 0.998 | D | 0.771 | deleterious | None | None | None | None | I |
| I/Q | 0.8852 | likely_pathogenic | 0.8752 | pathogenic | -1.642 | Destabilizing | 0.998 | D | 0.757 | deleterious | None | None | None | None | I |
| I/R | 0.8191 | likely_pathogenic | 0.7978 | pathogenic | -1.028 | Destabilizing | 0.998 | D | 0.766 | deleterious | None | None | None | None | I |
| I/S | 0.788 | likely_pathogenic | 0.7674 | pathogenic | -2.141 | Highly Destabilizing | 0.991 | D | 0.697 | prob.neutral | N | 0.492707449 | None | None | I |
| I/T | 0.7473 | likely_pathogenic | 0.7451 | pathogenic | -1.963 | Destabilizing | 0.939 | D | 0.643 | neutral | N | 0.492707449 | None | None | I |
| I/V | 0.0914 | likely_benign | 0.0883 | benign | -1.46 | Destabilizing | 0.02 | N | 0.198 | neutral | N | 0.510046612 | None | None | I |
| I/W | 0.9288 | likely_pathogenic | 0.9137 | pathogenic | -1.697 | Destabilizing | 0.999 | D | 0.686 | prob.neutral | None | None | None | None | I |
| I/Y | 0.7639 | likely_pathogenic | 0.7219 | pathogenic | -1.462 | Destabilizing | 0.998 | D | 0.706 | prob.neutral | None | None | None | None | I |
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.