Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 8759 | 26500;26501;26502 | chr2:178714499;178714498;178714497 | chr2:179579226;179579225;179579224 |
| N2AB | 8442 | 25549;25550;25551 | chr2:178714499;178714498;178714497 | chr2:179579226;179579225;179579224 |
| N2A | 7515 | 22768;22769;22770 | chr2:178714499;178714498;178714497 | chr2:179579226;179579225;179579224 |
| 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/M | None | None | 0.019 | N | 0.661 | 0.212 | 0.184867976434 | gnomAD-4.0.0 | 1.59203E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85933E-06 | 0 | 0 |
| I/T | rs199918663  |
-2.897 | None | D | 0.424 | 0.345 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.56437E-04 | None | 6.54E-05 | None | 0 | 7.83E-06 | 0 |
| I/T | rs199918663 |
-2.897 | None | D | 0.424 | 0.345 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 3.85951E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs199918663 |
-2.897 | None | D | 0.424 | 0.345 | None | gnomAD-4.0.0 | 2.29343E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.46312E-04 | None | 0 | 0 | 1.69548E-06 | 5.49113E-05 | 1.60154E-05 |
| I/V | rs1317485542 |
-1.533 | None | N | 0.199 | 0.079 | 0.154104182512 | gnomAD-2.1.1 | 1.43E-05 | None | None | None | None | N | None | 0 | 2.84E-05 | None | 0 | 0 | None | 0 | None | 8.02E-05 | 0 | 1.40885E-04 |
| I/V | rs1317485542 |
-1.533 | None | N | 0.199 | 0.079 | 0.154104182512 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 9.41E-05 | 0 | 0 | 0 | 0 |
| I/V | rs1317485542 |
-1.533 | None | N | 0.199 | 0.079 | 0.154104182512 | gnomAD-4.0.0 | 8.97144E-06 | None | None | None | None | N | None | 0 | 1.6956E-05 | None | 0 | 0 | None | 7.85275E-05 | 0 | 0 | 0 | 2.84592E-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 | 0.183 | likely_benign | 0.2935 | benign | -2.758 | Highly Destabilizing | 0.032 | N | 0.536 | neutral | None | None | None | None | N |
| I/C | 0.7673 | likely_pathogenic | 0.8556 | pathogenic | -1.954 | Destabilizing | 0.724 | D | 0.749 | deleterious | None | None | None | None | N |
| I/D | 0.9228 | likely_pathogenic | 0.9767 | pathogenic | -3.297 | Highly Destabilizing | 0.976 | D | 0.773 | deleterious | None | None | None | None | N |
| I/E | 0.8492 | likely_pathogenic | 0.9372 | pathogenic | -2.992 | Highly Destabilizing | 0.893 | D | 0.75 | deleterious | None | None | None | None | N |
| I/F | 0.2512 | likely_benign | 0.3636 | ambiguous | -1.614 | Destabilizing | 0.221 | N | 0.663 | neutral | N | 0.492701584 | None | None | N |
| I/G | 0.6692 | likely_pathogenic | 0.8565 | pathogenic | -3.369 | Highly Destabilizing | 0.269 | N | 0.738 | prob.delet. | None | None | None | None | N |
| I/H | 0.838 | likely_pathogenic | 0.9389 | pathogenic | -2.962 | Highly Destabilizing | 0.926 | D | 0.787 | deleterious | None | None | None | None | N |
| I/K | 0.7501 | likely_pathogenic | 0.8923 | pathogenic | -2.056 | Highly Destabilizing | 0.25 | N | 0.748 | deleterious | None | None | None | None | N |
| I/L | 0.1297 | likely_benign | 0.1726 | benign | -0.939 | Destabilizing | None | N | 0.205 | neutral | N | 0.490330274 | None | None | N |
| I/M | 0.1074 | likely_benign | 0.1346 | benign | -1.042 | Destabilizing | 0.019 | N | 0.661 | neutral | N | 0.511059329 | None | None | N |
| I/N | 0.6601 | likely_pathogenic | 0.83 | pathogenic | -2.661 | Highly Destabilizing | 0.968 | D | 0.781 | deleterious | D | 0.522922613 | None | None | N |
| I/P | 0.8406 | likely_pathogenic | 0.9449 | pathogenic | -1.534 | Destabilizing | 0.988 | D | 0.781 | deleterious | None | None | None | None | N |
| I/Q | 0.7667 | likely_pathogenic | 0.8986 | pathogenic | -2.366 | Highly Destabilizing | 0.971 | D | 0.795 | deleterious | None | None | None | None | N |
| I/R | 0.6383 | likely_pathogenic | 0.8304 | pathogenic | -1.989 | Destabilizing | 0.941 | D | 0.783 | deleterious | None | None | None | None | N |
| I/S | 0.3671 | ambiguous | 0.5658 | pathogenic | -3.304 | Highly Destabilizing | 0.122 | N | 0.692 | prob.neutral | N | 0.496171078 | None | None | N |
| I/T | 0.129 | likely_benign | 0.209 | benign | -2.837 | Highly Destabilizing | None | N | 0.424 | neutral | D | 0.532792972 | None | None | N |
| I/V | 0.0534 | likely_benign | 0.0549 | benign | -1.534 | Destabilizing | None | N | 0.199 | neutral | N | 0.382612871 | None | None | N |
| I/W | 0.8778 | likely_pathogenic | 0.96 | pathogenic | -2.054 | Highly Destabilizing | 0.978 | D | 0.777 | deleterious | None | None | None | None | N |
| I/Y | 0.7471 | likely_pathogenic | 0.8608 | pathogenic | -1.797 | Destabilizing | 0.109 | N | 0.741 | deleterious | 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.