Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31626 | 95101;95102;95103 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| N2AB | 29985 | 90178;90179;90180 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| N2A | 29058 | 87397;87398;87399 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| N2B | 22561 | 67906;67907;67908 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| Novex-1 | 22686 | 68281;68282;68283 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| Novex-2 | 22753 | 68482;68483;68484 | chr2:178546455;178546454;178546453 | chr2:179411182;179411181;179411180 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/I | rs542160074  |
0.334 | 0.991 | N | 0.558 | 0.405 | 0.648841342166 | gnomAD-2.1.1 | 1.62E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 1.30762E-04 | None | 0 | 0 | 0 |
| T/I | rs542160074 |
0.334 | 0.991 | N | 0.558 | 0.405 | 0.648841342166 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07211E-04 | 0 |
| T/I | rs542160074 |
0.334 | 0.991 | N | 0.558 | 0.405 | 0.648841342166 | gnomAD-4.0.0 | 7.68819E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 8.04203E-05 | 0 |
| T/N | rs542160074 |
-0.017 | 0.982 | N | 0.536 | 0.28 | 0.564208378351 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| T/N | rs542160074 |
-0.017 | 0.982 | N | 0.536 | 0.28 | 0.564208378351 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | rs542160074 |
-0.017 | 0.982 | N | 0.536 | 0.28 | 0.564208378351 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| T/N | rs542160074 |
-0.017 | 0.982 | N | 0.536 | 0.28 | 0.564208378351 | gnomAD-4.0.0 | 6.56737E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47024E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.1205 | likely_benign | 0.1303 | benign | -0.369 | Destabilizing | 0.76 | D | 0.501 | neutral | D | 0.523861271 | None | None | I |
| T/C | 0.4586 | ambiguous | 0.4816 | ambiguous | -0.406 | Destabilizing | 0.999 | D | 0.529 | neutral | None | None | None | None | I |
| T/D | 0.6797 | likely_pathogenic | 0.6832 | pathogenic | 0.297 | Stabilizing | 0.986 | D | 0.536 | neutral | None | None | None | None | I |
| T/E | 0.4862 | ambiguous | 0.4814 | ambiguous | 0.313 | Stabilizing | 0.986 | D | 0.537 | neutral | None | None | None | None | I |
| T/F | 0.3841 | ambiguous | 0.3688 | ambiguous | -0.522 | Destabilizing | 0.998 | D | 0.581 | neutral | None | None | None | None | I |
| T/G | 0.4554 | ambiguous | 0.4821 | ambiguous | -0.611 | Destabilizing | 0.91 | D | 0.503 | neutral | None | None | None | None | I |
| T/H | 0.3997 | ambiguous | 0.396 | ambiguous | -0.761 | Destabilizing | 0.999 | D | 0.55 | neutral | None | None | None | None | I |
| T/I | 0.1796 | likely_benign | 0.1914 | benign | 0.171 | Stabilizing | 0.991 | D | 0.558 | neutral | N | 0.5012752 | None | None | I |
| T/K | 0.3605 | ambiguous | 0.3447 | ambiguous | -0.354 | Destabilizing | 0.986 | D | 0.537 | neutral | None | None | None | None | I |
| T/L | 0.1231 | likely_benign | 0.1231 | benign | 0.171 | Stabilizing | 0.953 | D | 0.549 | neutral | None | None | None | None | I |
| T/M | 0.0951 | likely_benign | 0.0928 | benign | -0.006 | Destabilizing | 0.999 | D | 0.524 | neutral | None | None | None | None | I |
| T/N | 0.1985 | likely_benign | 0.2116 | benign | -0.42 | Destabilizing | 0.982 | D | 0.536 | neutral | N | 0.50873989 | None | None | I |
| T/P | 0.239 | likely_benign | 0.2431 | benign | 0.024 | Stabilizing | 0.991 | D | 0.556 | neutral | N | 0.513333372 | None | None | I |
| T/Q | 0.317 | likely_benign | 0.3112 | benign | -0.445 | Destabilizing | 0.993 | D | 0.543 | neutral | None | None | None | None | I |
| T/R | 0.3344 | likely_benign | 0.3064 | benign | -0.211 | Destabilizing | 0.986 | D | 0.556 | neutral | None | None | None | None | I |
| T/S | 0.1679 | likely_benign | 0.1811 | benign | -0.673 | Destabilizing | 0.17 | N | 0.221 | neutral | N | 0.483326153 | None | None | I |
| T/V | 0.1273 | likely_benign | 0.1334 | benign | 0.024 | Stabilizing | 0.953 | D | 0.521 | neutral | None | None | None | None | I |
| T/W | 0.7517 | likely_pathogenic | 0.7291 | pathogenic | -0.583 | Destabilizing | 0.999 | D | 0.631 | neutral | None | None | None | None | I |
| T/Y | 0.4314 | ambiguous | 0.4175 | ambiguous | -0.265 | Destabilizing | 0.998 | D | 0.583 | 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.