Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18976 | 57151;57152;57153 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| N2AB | 17335 | 52228;52229;52230 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| N2A | 16408 | 49447;49448;49449 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| N2B | 9911 | 29956;29957;29958 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| Novex-1 | 10036 | 30331;30332;30333 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| Novex-2 | 10103 | 30532;30533;30534 | chr2:178598784;178598783;178598782 | chr2:179463511;179463510;179463509 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/M | rs1333698664  |
-0.706 | 0.003 | N | 0.383 | 0.062 | 0.168933306366 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| L/M | rs1333698664 |
-0.706 | 0.003 | N | 0.383 | 0.062 | 0.168933306366 | gnomAD-4.0.0 | 1.36874E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31949E-05 | 0 |
| L/R | None | None | 0.437 | N | 0.628 | 0.107 | 0.245101548738 | gnomAD-4.0.0 | 1.59214E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43336E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.0995 | likely_benign | 0.1232 | benign | -0.95 | Destabilizing | 0.057 | N | 0.458 | neutral | None | None | None | None | N |
| L/C | 0.3825 | ambiguous | 0.4421 | ambiguous | -0.7 | Destabilizing | 0.96 | D | 0.469 | neutral | None | None | None | None | N |
| L/D | 0.3431 | ambiguous | 0.396 | ambiguous | -0.272 | Destabilizing | 0.507 | D | 0.667 | prob.neutral | None | None | None | None | N |
| L/E | 0.1724 | likely_benign | 0.1995 | benign | -0.345 | Destabilizing | 0.507 | D | 0.643 | neutral | None | None | None | None | N |
| L/F | 0.1197 | likely_benign | 0.1221 | benign | -0.799 | Destabilizing | 0.507 | D | 0.464 | neutral | None | None | None | None | N |
| L/G | 0.283 | likely_benign | 0.32 | benign | -1.161 | Destabilizing | 0.507 | D | 0.621 | neutral | None | None | None | None | N |
| L/H | 0.1582 | likely_benign | 0.1803 | benign | -0.34 | Destabilizing | 0.96 | D | 0.658 | prob.neutral | None | None | None | None | N |
| L/I | 0.0864 | likely_benign | 0.0861 | benign | -0.502 | Destabilizing | 0.004 | N | 0.334 | neutral | None | None | None | None | N |
| L/K | 0.1777 | likely_benign | 0.2042 | benign | -0.536 | Destabilizing | 0.227 | N | 0.583 | neutral | None | None | None | None | N |
| L/M | 0.0932 | likely_benign | 0.0963 | benign | -0.451 | Destabilizing | 0.003 | N | 0.383 | neutral | N | 0.465028319 | None | None | N |
| L/N | 0.195 | likely_benign | 0.2104 | benign | -0.295 | Destabilizing | 0.676 | D | 0.657 | prob.neutral | None | None | None | None | N |
| L/P | 0.0703 | likely_benign | 0.0925 | benign | -0.617 | Destabilizing | 0.001 | N | 0.528 | neutral | N | 0.405574584 | None | None | N |
| L/Q | 0.0944 | likely_benign | 0.1109 | benign | -0.527 | Destabilizing | 0.437 | N | 0.631 | neutral | N | 0.437879003 | None | None | N |
| L/R | 0.1666 | likely_benign | 0.2018 | benign | 0.069 | Stabilizing | 0.437 | N | 0.628 | neutral | N | 0.462545374 | None | None | N |
| L/S | 0.1142 | likely_benign | 0.1332 | benign | -0.831 | Destabilizing | 0.227 | N | 0.525 | neutral | None | None | None | None | N |
| L/T | 0.1225 | likely_benign | 0.1406 | benign | -0.79 | Destabilizing | 0.227 | N | 0.488 | neutral | None | None | None | None | N |
| L/V | 0.075 | likely_benign | 0.0801 | benign | -0.617 | Destabilizing | None | N | 0.249 | neutral | N | 0.453099172 | None | None | N |
| L/W | 0.259 | likely_benign | 0.281 | benign | -0.785 | Destabilizing | 0.96 | D | 0.674 | prob.neutral | None | None | None | None | N |
| L/Y | 0.2275 | likely_benign | 0.2407 | benign | -0.56 | Destabilizing | 0.676 | D | 0.507 | 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.