Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22696 | 68311;68312;68313 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| N2AB | 21055 | 63388;63389;63390 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| N2A | 20128 | 60607;60608;60609 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| N2B | 13631 | 41116;41117;41118 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| Novex-1 | 13756 | 41491;41492;41493 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| Novex-2 | 13823 | 41692;41693;41694 | chr2:178578944;178578943;178578942 | chr2:179443671;179443670;179443669 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/L | rs1245154926  |
-0.05 | 0.967 | N | 0.615 | 0.478 | 0.558264529485 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/L | rs1245154926 |
-0.05 | 0.967 | N | 0.615 | 0.478 | 0.558264529485 | gnomAD-4.0.0 | 1.59226E-06 | None | None | None | None | N | None | 0 | 2.2876E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/P | rs754821175 |
-0.165 | 0.025 | N | 0.293 | 0.331 | 0.223847106136 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/P | rs754821175 |
-0.165 | 0.025 | N | 0.293 | 0.331 | 0.223847106136 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/P | rs754821175 |
-0.165 | 0.025 | N | 0.293 | 0.331 | 0.223847106136 | gnomAD-4.0.0 | 2.56398E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.78907E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1201 | likely_benign | 0.1104 | benign | -0.379 | Destabilizing | 0.773 | D | 0.352 | neutral | N | 0.495063224 | None | None | N |
| S/C | 0.3075 | likely_benign | 0.2957 | benign | -0.272 | Destabilizing | 0.999 | D | 0.659 | neutral | None | None | None | None | N |
| S/D | 0.9012 | likely_pathogenic | 0.8967 | pathogenic | 0.033 | Stabilizing | 0.957 | D | 0.521 | neutral | None | None | None | None | N |
| S/E | 0.9062 | likely_pathogenic | 0.9048 | pathogenic | -0.06 | Destabilizing | 0.916 | D | 0.512 | neutral | None | None | None | None | N |
| S/F | 0.6723 | likely_pathogenic | 0.6422 | pathogenic | -0.928 | Destabilizing | 0.996 | D | 0.715 | prob.delet. | None | None | None | None | N |
| S/G | 0.2166 | likely_benign | 0.2092 | benign | -0.501 | Destabilizing | 0.916 | D | 0.383 | neutral | None | None | None | None | N |
| S/H | 0.8364 | likely_pathogenic | 0.8284 | pathogenic | -1.033 | Destabilizing | 0.999 | D | 0.654 | neutral | None | None | None | None | N |
| S/I | 0.6132 | likely_pathogenic | 0.5966 | pathogenic | -0.187 | Destabilizing | 0.987 | D | 0.719 | prob.delet. | None | None | None | None | N |
| S/K | 0.971 | likely_pathogenic | 0.9665 | pathogenic | -0.508 | Destabilizing | 0.916 | D | 0.523 | neutral | None | None | None | None | N |
| S/L | 0.2651 | likely_benign | 0.252 | benign | -0.187 | Destabilizing | 0.967 | D | 0.615 | neutral | N | 0.488860247 | None | None | N |
| S/M | 0.4393 | ambiguous | 0.4282 | ambiguous | 0.106 | Stabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| S/N | 0.5643 | likely_pathogenic | 0.554 | ambiguous | -0.237 | Destabilizing | 0.957 | D | 0.529 | neutral | None | None | None | None | N |
| S/P | 0.644 | likely_pathogenic | 0.6248 | pathogenic | -0.222 | Destabilizing | 0.025 | N | 0.293 | neutral | N | 0.515729285 | None | None | N |
| S/Q | 0.8674 | likely_pathogenic | 0.8575 | pathogenic | -0.52 | Destabilizing | 0.987 | D | 0.596 | neutral | None | None | None | None | N |
| S/R | 0.9587 | likely_pathogenic | 0.9527 | pathogenic | -0.283 | Destabilizing | 0.987 | D | 0.697 | prob.neutral | None | None | None | None | N |
| S/T | 0.1957 | likely_benign | 0.2 | benign | -0.342 | Destabilizing | 0.892 | D | 0.395 | neutral | N | 0.450677729 | None | None | N |
| S/V | 0.4852 | ambiguous | 0.4744 | ambiguous | -0.222 | Destabilizing | 0.987 | D | 0.628 | neutral | None | None | None | None | N |
| S/W | 0.7784 | likely_pathogenic | 0.7718 | pathogenic | -0.918 | Destabilizing | 0.999 | D | 0.721 | prob.delet. | None | None | None | None | N |
| S/Y | 0.6432 | likely_pathogenic | 0.6135 | pathogenic | -0.645 | Destabilizing | 0.996 | D | 0.712 | 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.