Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26986 | 81181;81182;81183 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| N2AB | 25345 | 76258;76259;76260 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| N2A | 24418 | 73477;73478;73479 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| N2B | 17921 | 53986;53987;53988 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| Novex-1 | 18046 | 54361;54362;54363 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| Novex-2 | 18113 | 54562;54563;54564 | chr2:178565176;178565175;178565174 | chr2:179429903;179429902;179429901 |
| 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/N | rs1389359522  |
-0.649 | 0.892 | N | 0.537 | 0.281 | 0.19670166235 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| S/N | rs1389359522 |
-0.649 | 0.892 | N | 0.537 | 0.281 | 0.19670166235 | gnomAD-4.0.0 | 1.16338E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.52929E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1692 | likely_benign | 0.1568 | benign | -0.596 | Destabilizing | 0.693 | D | 0.381 | neutral | None | None | None | None | N |
| S/C | 0.2185 | likely_benign | 0.2164 | benign | -0.325 | Destabilizing | 0.999 | D | 0.606 | neutral | N | 0.502176152 | None | None | N |
| S/D | 0.8179 | likely_pathogenic | 0.8014 | pathogenic | -0.761 | Destabilizing | 0.916 | D | 0.53 | neutral | None | None | None | None | N |
| S/E | 0.9297 | likely_pathogenic | 0.9213 | pathogenic | -0.627 | Destabilizing | 0.916 | D | 0.526 | neutral | None | None | None | None | N |
| S/F | 0.6595 | likely_pathogenic | 0.653 | pathogenic | -0.41 | Destabilizing | 0.987 | D | 0.682 | prob.neutral | None | None | None | None | N |
| S/G | 0.1555 | likely_benign | 0.1534 | benign | -0.947 | Destabilizing | 0.892 | D | 0.42 | neutral | N | 0.485657094 | None | None | N |
| S/H | 0.7477 | likely_pathogenic | 0.752 | pathogenic | -1.311 | Destabilizing | 0.999 | D | 0.603 | neutral | None | None | None | None | N |
| S/I | 0.7835 | likely_pathogenic | 0.7774 | pathogenic | 0.271 | Stabilizing | 0.967 | D | 0.697 | prob.neutral | N | 0.493617777 | None | None | N |
| S/K | 0.9537 | likely_pathogenic | 0.9562 | pathogenic | -0.304 | Destabilizing | 0.916 | D | 0.527 | neutral | None | None | None | None | N |
| S/L | 0.3158 | likely_benign | 0.3009 | benign | 0.271 | Stabilizing | 0.845 | D | 0.577 | neutral | None | None | None | None | N |
| S/M | 0.4828 | ambiguous | 0.4694 | ambiguous | 0.121 | Stabilizing | 0.999 | D | 0.609 | neutral | None | None | None | None | N |
| S/N | 0.4422 | ambiguous | 0.4257 | ambiguous | -0.684 | Destabilizing | 0.892 | D | 0.537 | neutral | N | 0.518326873 | None | None | N |
| S/P | 0.9717 | likely_pathogenic | 0.9718 | pathogenic | 0.016 | Stabilizing | 0.987 | D | 0.641 | neutral | None | None | None | None | N |
| S/Q | 0.8791 | likely_pathogenic | 0.874 | pathogenic | -0.539 | Destabilizing | 0.987 | D | 0.617 | neutral | None | None | None | None | N |
| S/R | 0.9355 | likely_pathogenic | 0.9382 | pathogenic | -0.554 | Destabilizing | 0.967 | D | 0.646 | neutral | N | 0.49637552 | None | None | N |
| S/T | 0.1273 | likely_benign | 0.1251 | benign | -0.455 | Destabilizing | 0.025 | N | 0.333 | neutral | N | 0.418661311 | None | None | N |
| S/V | 0.6824 | likely_pathogenic | 0.6688 | pathogenic | 0.016 | Stabilizing | 0.95 | D | 0.625 | neutral | None | None | None | None | N |
| S/W | 0.8101 | likely_pathogenic | 0.803 | pathogenic | -0.628 | Destabilizing | 0.999 | D | 0.673 | neutral | None | None | None | None | N |
| S/Y | 0.5875 | likely_pathogenic | 0.5704 | pathogenic | -0.207 | Destabilizing | 0.996 | D | 0.688 | prob.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.