Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2399 | 7420;7421;7422 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| N2AB | 2399 | 7420;7421;7422 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| N2A | 2399 | 7420;7421;7422 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| N2B | 2353 | 7282;7283;7284 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| Novex-1 | 2353 | 7282;7283;7284 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| Novex-2 | 2353 | 7282;7283;7284 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
| Novex-3 | 2399 | 7420;7421;7422 | chr2:178773973;178773972;178773971 | chr2:179638700;179638699;179638698 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | rs750522225  |
-0.392 | 0.998 | N | 0.501 | 0.539 | 0.461144880706 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/G | rs750522225 |
-0.392 | 0.998 | N | 0.501 | 0.539 | 0.461144880706 | gnomAD-4.0.0 | 3.18106E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86541E-05 | 0 |
| D/N | rs763147469 |
0.256 | 0.999 | N | 0.557 | 0.296 | 0.435152311215 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.82E-06 | 0 |
| D/N | rs763147469 |
0.256 | 0.999 | N | 0.557 | 0.296 | 0.435152311215 | gnomAD-4.0.0 | 1.59058E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85667E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1748 | likely_benign | 0.1747 | benign | 0.001 | Stabilizing | 0.999 | D | 0.537 | neutral | N | 0.510139467 | None | None | N |
| D/C | 0.6035 | likely_pathogenic | 0.6058 | pathogenic | -0.048 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| D/E | 0.1309 | likely_benign | 0.1313 | benign | -0.188 | Destabilizing | 0.767 | D | 0.337 | neutral | N | 0.508038287 | None | None | N |
| D/F | 0.6342 | likely_pathogenic | 0.6406 | pathogenic | -0.164 | Destabilizing | 1.0 | D | 0.691 | prob.neutral | None | None | None | None | N |
| D/G | 0.15 | likely_benign | 0.1489 | benign | -0.102 | Destabilizing | 0.998 | D | 0.501 | neutral | N | 0.50471455 | None | None | N |
| D/H | 0.2692 | likely_benign | 0.273 | benign | 0.38 | Stabilizing | 1.0 | D | 0.614 | neutral | D | 0.535436041 | None | None | N |
| D/I | 0.4154 | ambiguous | 0.4177 | ambiguous | 0.202 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| D/K | 0.2888 | likely_benign | 0.2864 | benign | 0.378 | Stabilizing | 0.999 | D | 0.546 | neutral | None | None | None | None | N |
| D/L | 0.3867 | ambiguous | 0.3796 | ambiguous | 0.202 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | None | None | None | None | N |
| D/M | 0.6016 | likely_pathogenic | 0.6074 | pathogenic | 0.071 | Stabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| D/N | 0.0958 | likely_benign | 0.0972 | benign | 0.307 | Stabilizing | 0.999 | D | 0.557 | neutral | N | 0.504120161 | None | None | N |
| D/P | 0.4288 | ambiguous | 0.4179 | ambiguous | 0.153 | Stabilizing | 1.0 | D | 0.587 | neutral | None | None | None | None | N |
| D/Q | 0.2856 | likely_benign | 0.282 | benign | 0.29 | Stabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | N |
| D/R | 0.3451 | ambiguous | 0.3495 | ambiguous | 0.573 | Stabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| D/S | 0.1054 | likely_benign | 0.106 | benign | 0.159 | Stabilizing | 0.997 | D | 0.488 | neutral | None | None | None | None | N |
| D/T | 0.2538 | likely_benign | 0.2577 | benign | 0.238 | Stabilizing | 1.0 | D | 0.581 | neutral | None | None | None | None | N |
| D/V | 0.2602 | likely_benign | 0.2619 | benign | 0.153 | Stabilizing | 0.999 | D | 0.692 | prob.neutral | D | 0.585685991 | None | None | N |
| D/W | 0.8825 | likely_pathogenic | 0.883 | pathogenic | -0.146 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | None | None | None | None | N |
| D/Y | 0.2902 | likely_benign | 0.2942 | benign | 0.053 | Stabilizing | 1.0 | D | 0.692 | prob.neutral | D | 0.611590558 | 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.