Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27585 | 82978;82979;82980 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| N2AB | 25944 | 78055;78056;78057 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| N2A | 25017 | 75274;75275;75276 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| N2B | 18520 | 55783;55784;55785 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| Novex-1 | 18645 | 56158;56159;56160 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| Novex-2 | 18712 | 56359;56360;56361 | chr2:178563379;178563378;178563377 | chr2:179428106;179428105;179428104 |
| 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/Y | rs72648215  |
-0.862 | 0.979 | N | 0.412 | 0.393 | None | gnomAD-2.1.1 | 9.31E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.03992E-04 | 0 |
| S/Y | rs72648215 |
-0.862 | 0.979 | N | 0.412 | 0.393 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.91221E-04 | 0 | 0 |
| S/Y | rs72648215 |
-0.862 | 0.979 | N | 0.412 | 0.393 | None | gnomAD-4.0.0 | 7.06567E-05 | None | None | None | None | N | None | 1.33558E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.23962E-05 | 1.09782E-05 | 4.804E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1304 | likely_benign | 0.12 | benign | -0.726 | Destabilizing | 0.472 | N | 0.317 | neutral | N | 0.480260009 | None | None | N |
| S/C | 0.1251 | likely_benign | 0.1283 | benign | -0.522 | Destabilizing | 0.994 | D | 0.373 | neutral | N | 0.508759518 | None | None | N |
| S/D | 0.4443 | ambiguous | 0.389 | ambiguous | -0.453 | Destabilizing | 0.373 | N | 0.265 | neutral | None | None | None | None | N |
| S/E | 0.6444 | likely_pathogenic | 0.5603 | ambiguous | -0.513 | Destabilizing | 0.009 | N | 0.109 | neutral | None | None | None | None | N |
| S/F | 0.2046 | likely_benign | 0.1811 | benign | -1.303 | Destabilizing | 0.979 | D | 0.413 | neutral | N | 0.490819847 | None | None | N |
| S/G | 0.127 | likely_benign | 0.1215 | benign | -0.864 | Destabilizing | 0.543 | D | 0.269 | neutral | None | None | None | None | N |
| S/H | 0.3526 | ambiguous | 0.33 | benign | -1.469 | Destabilizing | 0.953 | D | 0.385 | neutral | None | None | None | None | N |
| S/I | 0.3459 | ambiguous | 0.311 | benign | -0.476 | Destabilizing | 0.91 | D | 0.424 | neutral | None | None | None | None | N |
| S/K | 0.781 | likely_pathogenic | 0.7386 | pathogenic | -0.589 | Destabilizing | 0.59 | D | 0.241 | neutral | None | None | None | None | N |
| S/L | 0.1345 | likely_benign | 0.1251 | benign | -0.476 | Destabilizing | 0.742 | D | 0.38 | neutral | None | None | None | None | N |
| S/M | 0.2337 | likely_benign | 0.224 | benign | 0.034 | Stabilizing | 0.984 | D | 0.38 | neutral | None | None | None | None | N |
| S/N | 0.1473 | likely_benign | 0.1404 | benign | -0.461 | Destabilizing | 0.016 | N | 0.045 | neutral | None | None | None | None | N |
| S/P | 0.8737 | likely_pathogenic | 0.8115 | pathogenic | -0.532 | Destabilizing | 0.939 | D | 0.393 | neutral | N | 0.508506028 | None | None | N |
| S/Q | 0.5693 | likely_pathogenic | 0.5283 | ambiguous | -0.812 | Destabilizing | 0.59 | D | 0.355 | neutral | None | None | None | None | N |
| S/R | 0.7399 | likely_pathogenic | 0.6994 | pathogenic | -0.371 | Destabilizing | 0.742 | D | 0.39 | neutral | None | None | None | None | N |
| S/T | 0.0781 | likely_benign | 0.0797 | benign | -0.538 | Destabilizing | 0.012 | N | 0.051 | neutral | N | 0.448346713 | None | None | N |
| S/V | 0.3265 | likely_benign | 0.2976 | benign | -0.532 | Destabilizing | 0.742 | D | 0.377 | neutral | None | None | None | None | N |
| S/W | 0.4214 | ambiguous | 0.3603 | ambiguous | -1.236 | Destabilizing | 0.996 | D | 0.517 | neutral | None | None | None | None | N |
| S/Y | 0.2015 | likely_benign | 0.1718 | benign | -0.961 | Destabilizing | 0.979 | D | 0.412 | neutral | N | 0.499351769 | 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.