Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15088 | 45487;45488;45489 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| N2AB | 13447 | 40564;40565;40566 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| N2A | 12520 | 37783;37784;37785 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| N2B | 6023 | 18292;18293;18294 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| Novex-1 | 6148 | 18667;18668;18669 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| Novex-2 | 6215 | 18868;18869;18870 | chr2:178621562;178621561;178621560 | chr2:179486289;179486288;179486287 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs1281379374  |
-0.701 | None | N | 0.228 | 0.182 | 0.163833314356 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| V/L | rs1281379374 |
-0.701 | None | N | 0.228 | 0.182 | 0.163833314356 | gnomAD-3.1.2 | 6.59E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/L | rs1281379374 |
-0.701 | None | N | 0.228 | 0.182 | 0.163833314356 | gnomAD-4.0.0 | 6.58605E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.4728E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1678 | likely_benign | 0.2364 | benign | -2.175 | Highly Destabilizing | 0.027 | N | 0.595 | neutral | D | 0.530861734 | None | None | N |
| V/C | 0.6225 | likely_pathogenic | 0.6925 | pathogenic | -1.622 | Destabilizing | 0.935 | D | 0.618 | neutral | None | None | None | None | N |
| V/D | 0.4173 | ambiguous | 0.4696 | ambiguous | -2.734 | Highly Destabilizing | 0.317 | N | 0.675 | prob.neutral | D | 0.604560188 | None | None | N |
| V/E | 0.2776 | likely_benign | 0.3476 | ambiguous | -2.54 | Highly Destabilizing | 0.38 | N | 0.642 | neutral | None | None | None | None | N |
| V/F | 0.1485 | likely_benign | 0.148 | benign | -1.261 | Destabilizing | 0.317 | N | 0.651 | neutral | N | 0.509412443 | None | None | N |
| V/G | 0.28 | likely_benign | 0.3241 | benign | -2.677 | Highly Destabilizing | 0.317 | N | 0.681 | prob.neutral | D | 0.668363974 | None | None | N |
| V/H | 0.3773 | ambiguous | 0.4447 | ambiguous | -2.354 | Highly Destabilizing | 0.935 | D | 0.657 | neutral | None | None | None | None | N |
| V/I | 0.0648 | likely_benign | 0.0583 | benign | -0.781 | Destabilizing | None | N | 0.175 | neutral | N | 0.439566169 | None | None | N |
| V/K | 0.2486 | likely_benign | 0.3341 | benign | -1.96 | Destabilizing | 0.38 | N | 0.648 | neutral | None | None | None | None | N |
| V/L | 0.1107 | likely_benign | 0.1058 | benign | -0.781 | Destabilizing | None | N | 0.228 | neutral | N | 0.477694875 | None | None | N |
| V/M | 0.1062 | likely_benign | 0.1115 | benign | -0.78 | Destabilizing | 0.38 | N | 0.649 | neutral | None | None | None | None | N |
| V/N | 0.1905 | likely_benign | 0.2358 | benign | -2.188 | Highly Destabilizing | 0.38 | N | 0.681 | prob.neutral | None | None | None | None | N |
| V/P | 0.9071 | likely_pathogenic | 0.9179 | pathogenic | -1.219 | Destabilizing | 0.555 | D | 0.657 | neutral | None | None | None | None | N |
| V/Q | 0.245 | likely_benign | 0.3071 | benign | -2.08 | Highly Destabilizing | 0.555 | D | 0.631 | neutral | None | None | None | None | N |
| V/R | 0.2045 | likely_benign | 0.2626 | benign | -1.66 | Destabilizing | 0.38 | N | 0.681 | prob.neutral | None | None | None | None | N |
| V/S | 0.1712 | likely_benign | 0.2282 | benign | -2.775 | Highly Destabilizing | 0.081 | N | 0.648 | neutral | None | None | None | None | N |
| V/T | 0.0905 | likely_benign | 0.167 | benign | -2.456 | Highly Destabilizing | 0.001 | N | 0.47 | neutral | None | None | None | None | N |
| V/W | 0.6626 | likely_pathogenic | 0.693 | pathogenic | -1.769 | Destabilizing | 0.935 | D | 0.679 | prob.neutral | None | None | None | None | N |
| V/Y | 0.3881 | ambiguous | 0.4403 | ambiguous | -1.421 | Destabilizing | 0.555 | D | 0.665 | 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.