Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26968 | 81127;81128;81129 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| N2AB | 25327 | 76204;76205;76206 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| N2A | 24400 | 73423;73424;73425 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| N2B | 17903 | 53932;53933;53934 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| Novex-1 | 18028 | 54307;54308;54309 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| Novex-2 | 18095 | 54508;54509;54510 | chr2:178565230;178565229;178565228 | chr2:179429957;179429956;179429955 |
| 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/N | rs369539943  |
-0.252 | 0.942 | N | 0.627 | 0.424 | 0.823678856618 | 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 |
| I/N | rs369539943 |
-0.252 | 0.942 | N | 0.627 | 0.424 | 0.823678856618 | gnomAD-4.0.0 | 1.36856E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79905E-06 | 0 | 0 |
| I/T | rs369539943 |
-0.556 | 0.014 | N | 0.371 | 0.317 | None | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/T | rs369539943 |
-0.556 | 0.014 | N | 0.371 | 0.317 | None | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93424E-04 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs369539943 |
-0.556 | 0.014 | N | 0.371 | 0.317 | None | gnomAD-4.0.0 | 4.95829E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23065E-05 | None | 0 | 0 | 5.93371E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.4232 | ambiguous | 0.4428 | ambiguous | -1.227 | Destabilizing | 0.559 | D | 0.493 | neutral | None | None | None | None | N |
| I/C | 0.8019 | likely_pathogenic | 0.8054 | pathogenic | -0.804 | Destabilizing | 0.998 | D | 0.459 | neutral | None | None | None | None | N |
| I/D | 0.8978 | likely_pathogenic | 0.898 | pathogenic | 0.181 | Stabilizing | 0.956 | D | 0.619 | neutral | None | None | None | None | N |
| I/E | 0.7894 | likely_pathogenic | 0.7772 | pathogenic | 0.226 | Stabilizing | 0.956 | D | 0.617 | neutral | None | None | None | None | N |
| I/F | 0.2385 | likely_benign | 0.2347 | benign | -0.599 | Destabilizing | 0.97 | D | 0.335 | neutral | N | 0.493859538 | None | None | N |
| I/G | 0.842 | likely_pathogenic | 0.8453 | pathogenic | -1.571 | Destabilizing | 0.956 | D | 0.585 | neutral | None | None | None | None | N |
| I/H | 0.6705 | likely_pathogenic | 0.6609 | pathogenic | -0.681 | Destabilizing | 0.998 | D | 0.647 | neutral | None | None | None | None | N |
| I/K | 0.6326 | likely_pathogenic | 0.5994 | pathogenic | -0.529 | Destabilizing | 0.956 | D | 0.614 | neutral | None | None | None | None | N |
| I/L | 0.1613 | likely_benign | 0.1563 | benign | -0.358 | Destabilizing | 0.294 | N | 0.389 | neutral | N | 0.484211526 | None | None | N |
| I/M | 0.1247 | likely_benign | 0.1272 | benign | -0.429 | Destabilizing | 0.988 | D | 0.353 | neutral | N | 0.510900609 | None | None | N |
| I/N | 0.4421 | ambiguous | 0.4491 | ambiguous | -0.41 | Destabilizing | 0.942 | D | 0.627 | neutral | N | 0.503678 | None | None | N |
| I/P | 0.9765 | likely_pathogenic | 0.977 | pathogenic | -0.615 | Destabilizing | 0.978 | D | 0.626 | neutral | None | None | None | None | N |
| I/Q | 0.6307 | likely_pathogenic | 0.6082 | pathogenic | -0.462 | Destabilizing | 0.978 | D | 0.636 | neutral | None | None | None | None | N |
| I/R | 0.5019 | ambiguous | 0.4797 | ambiguous | -0.163 | Destabilizing | 0.956 | D | 0.629 | neutral | None | None | None | None | N |
| I/S | 0.4219 | ambiguous | 0.4336 | ambiguous | -1.201 | Destabilizing | 0.698 | D | 0.532 | neutral | D | 0.528304298 | None | None | N |
| I/T | 0.1689 | likely_benign | 0.1888 | benign | -1.026 | Destabilizing | 0.014 | N | 0.371 | neutral | N | 0.473488379 | None | None | N |
| I/V | 0.08 | likely_benign | 0.0782 | benign | -0.615 | Destabilizing | 0.006 | N | 0.207 | neutral | N | 0.48193729 | None | None | N |
| I/W | 0.8844 | likely_pathogenic | 0.8807 | pathogenic | -0.647 | Destabilizing | 0.998 | D | 0.716 | prob.delet. | None | None | None | None | N |
| I/Y | 0.6852 | likely_pathogenic | 0.6778 | pathogenic | -0.394 | Destabilizing | 0.993 | D | 0.422 | 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.