Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18229 | 54910;54911;54912 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| N2AB | 16588 | 49987;49988;49989 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| N2A | 15661 | 47206;47207;47208 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| N2B | 9164 | 27715;27716;27717 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| Novex-1 | 9289 | 28090;28091;28092 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| Novex-2 | 9356 | 28291;28292;28293 | chr2:178604002;178604001;178604000 | chr2:179468729;179468728;179468727 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/L | rs116142642  |
-0.269 | None | N | 0.083 | 0.107 | 0.193865811164 | gnomAD-2.1.1 | 2.01E-05 | None | None | None | None | I | None | 0 | 1.4486E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/L | rs116142642 |
-0.269 | None | N | 0.083 | 0.107 | 0.193865811164 | gnomAD-4.0.0 | 3.4227E-06 | None | None | None | None | I | None | 0 | 1.11842E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/M | rs116142642 |
-0.349 | 0.808 | N | 0.28 | 0.055 | None | gnomAD-2.1.1 | 1.39335E-04 | None | None | None | None | I | None | 1.65508E-04 | 0 | None | 0 | 8.73946E-04 | None | 3.59501E-04 | None | 0 | 3.13E-05 | 4.21467E-04 |
| V/M | rs116142642 |
-0.349 | 0.808 | N | 0.28 | 0.055 | None | gnomAD-3.1.2 | 1.11891E-04 | None | None | None | None | I | None | 2.41464E-04 | 0 | 0 | 0 | 5.83885E-04 | None | 0 | 0 | 5.89E-05 | 0 | 0 |
| V/M | rs116142642 |
-0.349 | 0.808 | N | 0.28 | 0.055 | None | 1000 genomes | 5.99042E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 2E-03 | 0 | None | None | None | 0 | None |
| V/M | rs116142642 |
-0.349 | 0.808 | N | 0.28 | 0.055 | None | gnomAD-4.0.0 | 6.94407E-05 | None | None | None | None | I | None | 2.80187E-04 | 0 | None | 0 | 5.80435E-04 | None | 0 | 0 | 2.20491E-05 | 3.07591E-04 | 1.76186E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2757 | likely_benign | 0.2042 | benign | -1.776 | Destabilizing | 0.081 | N | 0.188 | neutral | N | 0.41698923 | None | None | I |
| V/C | 0.6548 | likely_pathogenic | 0.6529 | pathogenic | -1.545 | Destabilizing | 0.859 | D | 0.242 | neutral | None | None | None | None | I |
| V/D | 0.7593 | likely_pathogenic | 0.6906 | pathogenic | -2.3 | Highly Destabilizing | 0.859 | D | 0.309 | neutral | None | None | None | None | I |
| V/E | 0.5902 | likely_pathogenic | 0.4931 | ambiguous | -2.055 | Highly Destabilizing | 0.602 | D | 0.349 | neutral | N | 0.394632445 | None | None | I |
| V/F | 0.2452 | likely_benign | 0.1877 | benign | -0.991 | Destabilizing | 0.124 | N | 0.273 | neutral | None | None | None | None | I |
| V/G | 0.3712 | ambiguous | 0.3013 | benign | -2.352 | Highly Destabilizing | 0.301 | N | 0.333 | neutral | N | 0.459163926 | None | None | I |
| V/H | 0.7616 | likely_pathogenic | 0.6919 | pathogenic | -2.224 | Highly Destabilizing | 0.958 | D | 0.237 | neutral | None | None | None | None | I |
| V/I | 0.0904 | likely_benign | 0.078 | benign | -0.165 | Destabilizing | None | N | 0.069 | neutral | None | None | None | None | I |
| V/K | 0.641 | likely_pathogenic | 0.5545 | ambiguous | -1.343 | Destabilizing | 0.364 | N | 0.333 | neutral | None | None | None | None | I |
| V/L | 0.2312 | likely_benign | 0.1638 | benign | -0.165 | Destabilizing | None | N | 0.083 | neutral | N | 0.343590336 | None | None | I |
| V/M | 0.1855 | likely_benign | 0.1352 | benign | -0.439 | Destabilizing | 0.808 | D | 0.28 | neutral | N | 0.422416479 | None | None | I |
| V/N | 0.4944 | ambiguous | 0.4236 | ambiguous | -1.716 | Destabilizing | 0.859 | D | 0.287 | neutral | None | None | None | None | I |
| V/P | 0.6414 | likely_pathogenic | 0.5812 | pathogenic | -0.673 | Destabilizing | 0.859 | D | 0.281 | neutral | None | None | None | None | I |
| V/Q | 0.5054 | ambiguous | 0.4224 | ambiguous | -1.498 | Destabilizing | 0.859 | D | 0.269 | neutral | None | None | None | None | I |
| V/R | 0.5573 | ambiguous | 0.4753 | ambiguous | -1.367 | Destabilizing | 0.667 | D | 0.309 | neutral | None | None | None | None | I |
| V/S | 0.4169 | ambiguous | 0.3239 | benign | -2.376 | Highly Destabilizing | 0.364 | N | 0.351 | neutral | None | None | None | None | I |
| V/T | 0.2405 | likely_benign | 0.1917 | benign | -1.967 | Destabilizing | 0.22 | N | 0.171 | neutral | None | None | None | None | I |
| V/W | 0.7993 | likely_pathogenic | 0.6978 | pathogenic | -1.52 | Destabilizing | None | N | 0.205 | neutral | None | None | None | None | I |
| V/Y | 0.617 | likely_pathogenic | 0.5681 | pathogenic | -1.082 | Destabilizing | 0.22 | N | 0.335 | neutral | None | None | None | None | I |
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.