Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30316 | 91171;91172;91173 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| N2AB | 28675 | 86248;86249;86250 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| N2A | 27748 | 83467;83468;83469 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| N2B | 21251 | 63976;63977;63978 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| Novex-1 | 21376 | 64351;64352;64353 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| Novex-2 | 21443 | 64552;64553;64554 | chr2:178551954;178551953;178551952 | chr2:179416681;179416680;179416679 |
| 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/N | rs140531141  |
None | 0.989 | N | 0.849 | 0.389 | 0.839648149646 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | rs140531141 |
None | 0.989 | N | 0.849 | 0.389 | 0.839648149646 | gnomAD-4.0.0 | 1.24018E-06 | None | None | None | None | N | None | 1.33483E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 8.4825E-07 | 0 | 0 |
| I/T | rs140531141 |
-1.431 | 0.799 | N | 0.606 | 0.352 | None | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | N | None | 1.29082E-04 | 0 | None | 0 | 1.67112E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs140531141 |
-1.431 | 0.799 | N | 0.606 | 0.352 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.82E-05 | 0 | 0 | 0 | 1.92976E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs140531141 |
-1.431 | 0.799 | N | 0.606 | 0.352 | None | 1000 genomes | 3.99361E-04 | None | None | None | None | N | None | 1.5E-03 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| I/T | rs140531141 |
-1.431 | 0.799 | N | 0.606 | 0.352 | None | gnomAD-4.0.0 | 4.3403E-06 | None | None | None | None | N | None | 2.66532E-05 | 0 | None | 0 | 8.9222E-05 | None | 0 | 0 | 8.48256E-07 | 0 | 0 |
| I/V | None | None | 0.002 | N | 0.147 | 0.072 | 0.550128394979 | gnomAD-4.0.0 | 3.60097E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-06 | 0 | 3.66327E-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 | 0.2494 | likely_benign | 0.2784 | benign | -1.943 | Destabilizing | 0.522 | D | 0.562 | neutral | None | None | None | None | N |
| I/C | 0.6626 | likely_pathogenic | 0.6689 | pathogenic | -1.27 | Destabilizing | 0.998 | D | 0.671 | prob.neutral | None | None | None | None | N |
| I/D | 0.9231 | likely_pathogenic | 0.9291 | pathogenic | -1.764 | Destabilizing | 0.991 | D | 0.843 | deleterious | None | None | None | None | N |
| I/E | 0.815 | likely_pathogenic | 0.8082 | pathogenic | -1.539 | Destabilizing | 0.974 | D | 0.811 | deleterious | None | None | None | None | N |
| I/F | 0.1913 | likely_benign | 0.2284 | benign | -1.13 | Destabilizing | 0.933 | D | 0.554 | neutral | N | 0.495842376 | None | None | N |
| I/G | 0.7656 | likely_pathogenic | 0.7889 | pathogenic | -2.414 | Highly Destabilizing | 0.974 | D | 0.768 | deleterious | None | None | None | None | N |
| I/H | 0.7086 | likely_pathogenic | 0.7347 | pathogenic | -1.582 | Destabilizing | 0.998 | D | 0.847 | deleterious | None | None | None | None | N |
| I/K | 0.6405 | likely_pathogenic | 0.6795 | pathogenic | -1.316 | Destabilizing | 0.974 | D | 0.811 | deleterious | None | None | None | None | N |
| I/L | 0.1258 | likely_benign | 0.1412 | benign | -0.589 | Destabilizing | 0.264 | N | 0.357 | neutral | N | 0.461479087 | None | None | N |
| I/M | 0.0992 | likely_benign | 0.1004 | benign | -0.659 | Destabilizing | 0.966 | D | 0.577 | neutral | N | 0.490436557 | None | None | N |
| I/N | 0.6267 | likely_pathogenic | 0.6358 | pathogenic | -1.742 | Destabilizing | 0.989 | D | 0.849 | deleterious | N | 0.47621522 | None | None | N |
| I/P | 0.9188 | likely_pathogenic | 0.9402 | pathogenic | -1.023 | Destabilizing | 0.991 | D | 0.845 | deleterious | None | None | None | None | N |
| I/Q | 0.663 | likely_pathogenic | 0.6618 | pathogenic | -1.545 | Destabilizing | 0.991 | D | 0.861 | deleterious | None | None | None | None | N |
| I/R | 0.533 | ambiguous | 0.5837 | pathogenic | -1.215 | Destabilizing | 0.974 | D | 0.856 | deleterious | None | None | None | None | N |
| I/S | 0.4211 | ambiguous | 0.4477 | ambiguous | -2.417 | Highly Destabilizing | 0.966 | D | 0.747 | deleterious | N | 0.475201262 | None | None | N |
| I/T | 0.1354 | likely_benign | 0.1427 | benign | -2.036 | Highly Destabilizing | 0.799 | D | 0.606 | neutral | N | 0.49445551 | None | None | N |
| I/V | 0.0566 | likely_benign | 0.0581 | benign | -1.023 | Destabilizing | 0.002 | N | 0.147 | neutral | N | 0.415146577 | None | None | N |
| I/W | 0.8735 | likely_pathogenic | 0.902 | pathogenic | -1.309 | Destabilizing | 0.998 | D | 0.829 | deleterious | None | None | None | None | N |
| I/Y | 0.6905 | likely_pathogenic | 0.7262 | pathogenic | -1.027 | Destabilizing | 0.974 | D | 0.689 | prob.delet. | 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.