Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33458 | 100597;100598;100599 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| N2AB | 31817 | 95674;95675;95676 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| N2A | 30890 | 92893;92894;92895 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| N2B | 24393 | 73402;73403;73404 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| Novex-1 | 24518 | 73777;73778;73779 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| Novex-2 | 24585 | 73978;73979;73980 | chr2:178536375;178536374;178536373 | chr2:179401102;179401101;179401100 |
| 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 | rs72648283  |
-1.445 | 0.37 | N | 0.241 | 0.224 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| I/T | rs72648283 |
-1.445 | 0.37 | N | 0.241 | 0.224 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07125E-04 | 0 |
| I/T | rs72648283 |
-1.445 | 0.37 | N | 0.241 | 0.224 | None | gnomAD-4.0.0 | 8.67593E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32361E-06 | 3.29395E-05 | 0 |
| I/V | rs2154137413 |
None | 0.887 | N | 0.297 | 0.134 | 0.414798848334 | gnomAD-4.0.0 | 1.5915E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77316E-05 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.2402 | likely_benign | 0.208 | benign | -1.431 | Destabilizing | 0.983 | D | 0.425 | neutral | None | None | None | None | N |
| I/C | 0.7564 | likely_pathogenic | 0.6818 | pathogenic | -0.988 | Destabilizing | 1.0 | D | 0.561 | neutral | None | None | None | None | N |
| I/D | 0.6936 | likely_pathogenic | 0.6588 | pathogenic | -0.874 | Destabilizing | 0.998 | D | 0.68 | prob.neutral | None | None | None | None | N |
| I/E | 0.4573 | ambiguous | 0.4361 | ambiguous | -0.848 | Destabilizing | 0.998 | D | 0.679 | prob.neutral | None | None | None | None | N |
| I/F | 0.256 | likely_benign | 0.2211 | benign | -0.895 | Destabilizing | 0.999 | D | 0.53 | neutral | N | 0.499933113 | None | None | N |
| I/G | 0.6429 | likely_pathogenic | 0.5744 | pathogenic | -1.743 | Destabilizing | 0.998 | D | 0.651 | neutral | None | None | None | None | N |
| I/H | 0.5269 | ambiguous | 0.4745 | ambiguous | -0.724 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| I/K | 0.2822 | likely_benign | 0.2711 | benign | -1.004 | Destabilizing | 0.995 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/L | 0.1221 | likely_benign | 0.1024 | benign | -0.646 | Destabilizing | 0.948 | D | 0.315 | neutral | N | 0.475746745 | None | None | N |
| I/M | 0.1214 | likely_benign | 0.1015 | benign | -0.69 | Destabilizing | 0.999 | D | 0.519 | neutral | N | 0.499933113 | None | None | N |
| I/N | 0.3331 | likely_benign | 0.2879 | benign | -0.94 | Destabilizing | 0.997 | D | 0.69 | prob.neutral | N | 0.480307203 | None | None | N |
| I/P | 0.6819 | likely_pathogenic | 0.663 | pathogenic | -0.877 | Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/Q | 0.3254 | likely_benign | 0.3018 | benign | -1.055 | Destabilizing | 0.999 | D | 0.681 | prob.neutral | None | None | None | None | N |
| I/R | 0.2346 | likely_benign | 0.2304 | benign | -0.429 | Destabilizing | 0.998 | D | 0.683 | prob.neutral | None | None | None | None | N |
| I/S | 0.2834 | likely_benign | 0.2458 | benign | -1.528 | Destabilizing | 0.956 | D | 0.495 | neutral | N | 0.461374725 | None | None | N |
| I/T | 0.1389 | likely_benign | 0.1164 | benign | -1.376 | Destabilizing | 0.37 | N | 0.241 | neutral | N | 0.391821427 | None | None | N |
| I/V | 0.098 | likely_benign | 0.0814 | benign | -0.877 | Destabilizing | 0.887 | D | 0.297 | neutral | N | 0.45993193 | None | None | N |
| I/W | 0.7758 | likely_pathogenic | 0.748 | pathogenic | -0.942 | Destabilizing | 1.0 | D | 0.693 | prob.neutral | None | None | None | None | N |
| I/Y | 0.59 | likely_pathogenic | 0.5663 | pathogenic | -0.726 | Destabilizing | 0.999 | D | 0.56 | 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.