Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17478 | 52657;52658;52659 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| N2AB | 15837 | 47734;47735;47736 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| N2A | 14910 | 44953;44954;44955 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| N2B | 8413 | 25462;25463;25464 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| Novex-1 | 8538 | 25837;25838;25839 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| Novex-2 | 8605 | 26038;26039;26040 | chr2:178608451;178608450;178608449 | chr2:179473178;179473177;179473176 |
| 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 | rs554368924  |
-0.349 | 0.304 | N | 0.412 | 0.033 | 0.289474373501 | gnomAD-2.1.1 | 2.98E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.74E-05 | 1.46113E-04 |
| I/M | rs554368924 |
-0.349 | 0.304 | N | 0.412 | 0.033 | 0.289474373501 | gnomAD-3.1.2 | 3.95E-05 | None | None | None | None | N | None | 2.41E-05 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| I/M | rs554368924 |
-0.349 | 0.304 | N | 0.412 | 0.033 | 0.289474373501 | gnomAD-4.0.0 | 1.80627E-05 | None | None | None | None | N | None | 1.3389E-05 | 3.38834E-05 | None | 0 | 0 | None | 0 | 0 | 2.04165E-05 | 0 | 3.21906E-05 |
| I/T | rs1178377744 |
-0.663 | 0.001 | N | 0.159 | 0.052 | 0.1749357433 | gnomAD-2.1.1 | 1.27E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.46E-05 | None | 0 | 1.88E-05 | 0 |
| I/T | rs1178377744 |
-0.663 | 0.001 | N | 0.159 | 0.052 | 0.1749357433 | gnomAD-4.0.0 | 8.0622E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.15764E-05 | 1.46024E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1177 | likely_benign | 0.0992 | benign | -1.204 | Destabilizing | 0.015 | N | 0.267 | neutral | None | None | None | None | N |
| I/C | 0.4596 | ambiguous | 0.3635 | ambiguous | -0.792 | Destabilizing | 0.781 | D | 0.426 | neutral | None | None | None | None | N |
| I/D | 0.2588 | likely_benign | 0.2086 | benign | -0.739 | Destabilizing | None | N | 0.35 | neutral | None | None | None | None | N |
| I/E | 0.1673 | likely_benign | 0.1485 | benign | -0.778 | Destabilizing | None | N | 0.301 | neutral | None | None | None | None | N |
| I/F | 0.1168 | likely_benign | 0.1052 | benign | -0.837 | Destabilizing | 0.059 | N | 0.393 | neutral | N | 0.446157344 | None | None | N |
| I/G | 0.3977 | ambiguous | 0.3268 | benign | -1.459 | Destabilizing | 0.033 | N | 0.294 | neutral | None | None | None | None | N |
| I/H | 0.2182 | likely_benign | 0.1767 | benign | -0.634 | Destabilizing | 0.367 | N | 0.479 | neutral | None | None | None | None | N |
| I/K | 0.1481 | likely_benign | 0.1233 | benign | -0.91 | Destabilizing | 0.033 | N | 0.285 | neutral | None | None | None | None | N |
| I/L | 0.089 | likely_benign | 0.0798 | benign | -0.607 | Destabilizing | None | N | 0.063 | neutral | N | 0.406926952 | None | None | N |
| I/M | 0.0846 | likely_benign | 0.0794 | benign | -0.564 | Destabilizing | 0.304 | N | 0.412 | neutral | N | 0.451717879 | None | None | N |
| I/N | 0.1209 | likely_benign | 0.0938 | benign | -0.708 | Destabilizing | None | N | 0.326 | neutral | N | 0.42939838 | None | None | N |
| I/P | 0.8394 | likely_pathogenic | 0.7921 | pathogenic | -0.773 | Destabilizing | 0.251 | N | 0.503 | neutral | None | None | None | None | N |
| I/Q | 0.1622 | likely_benign | 0.1335 | benign | -0.912 | Destabilizing | 0.006 | N | 0.335 | neutral | None | None | None | None | N |
| I/R | 0.121 | likely_benign | 0.1031 | benign | -0.282 | Destabilizing | 0.142 | N | 0.455 | neutral | None | None | None | None | N |
| I/S | 0.1064 | likely_benign | 0.0911 | benign | -1.213 | Destabilizing | 0.011 | N | 0.252 | neutral | N | 0.420602751 | None | None | N |
| I/T | 0.0734 | likely_benign | 0.0697 | benign | -1.143 | Destabilizing | 0.001 | N | 0.159 | neutral | N | 0.394821659 | None | None | N |
| I/V | 0.0586 | likely_benign | 0.0564 | benign | -0.773 | Destabilizing | 0.001 | N | 0.06 | neutral | N | 0.382356581 | None | None | N |
| I/W | 0.5872 | likely_pathogenic | 0.5302 | ambiguous | -0.872 | Destabilizing | 0.931 | D | 0.466 | neutral | None | None | None | None | N |
| I/Y | 0.3366 | likely_benign | 0.2947 | benign | -0.667 | Destabilizing | 0.251 | N | 0.502 | 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.