Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30854 | 92785;92786;92787 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| N2AB | 29213 | 87862;87863;87864 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| N2A | 28286 | 85081;85082;85083 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| N2B | 21789 | 65590;65591;65592 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| Novex-1 | 21914 | 65965;65966;65967 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| Novex-2 | 21981 | 66166;66167;66168 | chr2:178549066;178549065;178549064 | chr2:179413793;179413792;179413791 |
| 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/T | rs368427408  |
-0.987 | 0.008 | N | 0.263 | 0.258 | None | gnomAD-2.1.1 | 3.93E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 9.8E-05 | None | 0 | 6.25E-05 | 0 |
| I/T | rs368427408 |
-0.987 | 0.008 | N | 0.263 | 0.258 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.35E-05 | 0 | 0 |
| I/T | rs368427408 |
-0.987 | 0.008 | N | 0.263 | 0.258 | None | gnomAD-4.0.0 | 2.16892E-05 | None | None | None | None | I | None | 1.33508E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69516E-05 | 1.53714E-04 | 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 | 0.1396 | likely_benign | 0.144 | benign | -0.875 | Destabilizing | 0.415 | N | 0.575 | neutral | None | None | None | None | I |
| I/C | 0.6359 | likely_pathogenic | 0.6698 | pathogenic | -0.701 | Destabilizing | 0.996 | D | 0.617 | neutral | None | None | None | None | I |
| I/D | 0.6719 | likely_pathogenic | 0.714 | pathogenic | -0.22 | Destabilizing | 0.923 | D | 0.664 | neutral | None | None | None | None | I |
| I/E | 0.5181 | ambiguous | 0.5605 | ambiguous | -0.284 | Destabilizing | 0.923 | D | 0.648 | neutral | None | None | None | None | I |
| I/F | 0.146 | likely_benign | 0.1639 | benign | -0.663 | Destabilizing | 0.901 | D | 0.541 | neutral | N | 0.489713302 | None | None | I |
| I/G | 0.5218 | ambiguous | 0.557 | ambiguous | -1.09 | Destabilizing | 0.923 | D | 0.597 | neutral | None | None | None | None | I |
| I/H | 0.4397 | ambiguous | 0.488 | ambiguous | -0.284 | Destabilizing | 0.996 | D | 0.696 | prob.neutral | None | None | None | None | I |
| I/K | 0.3223 | likely_benign | 0.3426 | ambiguous | -0.53 | Destabilizing | 0.923 | D | 0.607 | neutral | None | None | None | None | I |
| I/L | 0.0975 | likely_benign | 0.0987 | benign | -0.411 | Destabilizing | 0.075 | N | 0.239 | neutral | N | 0.422875052 | None | None | I |
| I/M | 0.0929 | likely_benign | 0.0939 | benign | -0.429 | Destabilizing | 0.19 | N | 0.289 | neutral | N | 0.467254181 | None | None | I |
| I/N | 0.3238 | likely_benign | 0.3425 | ambiguous | -0.341 | Destabilizing | 0.901 | D | 0.685 | prob.neutral | D | 0.523385976 | None | None | I |
| I/P | 0.6905 | likely_pathogenic | 0.7253 | pathogenic | -0.531 | Destabilizing | 0.961 | D | 0.686 | prob.neutral | None | None | None | None | I |
| I/Q | 0.382 | ambiguous | 0.4069 | ambiguous | -0.548 | Destabilizing | 0.961 | D | 0.693 | prob.neutral | None | None | None | None | I |
| I/R | 0.2182 | likely_benign | 0.2413 | benign | 0.047 | Stabilizing | 0.923 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/S | 0.1954 | likely_benign | 0.2088 | benign | -0.867 | Destabilizing | 0.565 | D | 0.575 | neutral | N | 0.444866477 | None | None | I |
| I/T | 0.0633 | likely_benign | 0.062 | benign | -0.819 | Destabilizing | 0.008 | N | 0.263 | neutral | N | 0.372214158 | None | None | I |
| I/V | 0.0971 | likely_benign | 0.0992 | benign | -0.531 | Destabilizing | 0.19 | N | 0.267 | neutral | N | 0.487329176 | None | None | I |
| I/W | 0.6535 | likely_pathogenic | 0.6975 | pathogenic | -0.675 | Destabilizing | 0.996 | D | 0.771 | deleterious | None | None | None | None | I |
| I/Y | 0.5 | ambiguous | 0.5497 | ambiguous | -0.446 | Destabilizing | 0.961 | D | 0.635 | 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.