Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16592 | 49999;50000;50001 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| N2AB | 14951 | 45076;45077;45078 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| N2A | 14024 | 42295;42296;42297 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| N2B | 7527 | 22804;22805;22806 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| Novex-1 | 7652 | 23179;23180;23181 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| Novex-2 | 7719 | 23380;23381;23382 | chr2:178612947;178612946;178612945 | chr2:179477674;179477673;179477672 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/R | rs1017317726  |
-0.234 | 0.999 | N | 0.563 | 0.332 | 0.227934060464 | gnomAD-2.1.1 | 4.03E-05 | None | None | None | None | N | None | 0 | 2.90461E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| K/R | rs1017317726 |
-0.234 | 0.999 | N | 0.563 | 0.332 | 0.227934060464 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| K/R | rs1017317726 |
-0.234 | 0.999 | N | 0.563 | 0.332 | 0.227934060464 | gnomAD-4.0.0 | 1.41114E-05 | None | None | None | None | N | None | 0 | 1.86687E-04 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.8636 | likely_pathogenic | 0.9042 | pathogenic | -0.69 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | N |
| K/C | 0.943 | likely_pathogenic | 0.9537 | pathogenic | -0.616 | Destabilizing | 1.0 | D | 0.718 | prob.delet. | None | None | None | None | N |
| K/D | 0.9718 | likely_pathogenic | 0.978 | pathogenic | -0.154 | Destabilizing | 1.0 | D | 0.763 | deleterious | None | None | None | None | N |
| K/E | 0.709 | likely_pathogenic | 0.7845 | pathogenic | -0.025 | Destabilizing | 0.999 | D | 0.601 | neutral | N | 0.458361826 | None | None | N |
| K/F | 0.9773 | likely_pathogenic | 0.9826 | pathogenic | -0.335 | Destabilizing | 1.0 | D | 0.719 | prob.delet. | None | None | None | None | N |
| K/G | 0.9224 | likely_pathogenic | 0.9448 | pathogenic | -1.065 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/H | 0.7438 | likely_pathogenic | 0.7681 | pathogenic | -1.328 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | N |
| K/I | 0.8412 | likely_pathogenic | 0.878 | pathogenic | 0.286 | Stabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| K/L | 0.7396 | likely_pathogenic | 0.7871 | pathogenic | 0.286 | Stabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| K/M | 0.6738 | likely_pathogenic | 0.7553 | pathogenic | 0.08 | Stabilizing | 1.0 | D | 0.668 | neutral | D | 0.65830872 | None | None | N |
| K/N | 0.9323 | likely_pathogenic | 0.9464 | pathogenic | -0.566 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.506561343 | None | None | N |
| K/P | 0.886 | likely_pathogenic | 0.9158 | pathogenic | -0.01 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| K/Q | 0.4304 | ambiguous | 0.4854 | ambiguous | -0.562 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | N | 0.472040702 | None | None | N |
| K/R | 0.16 | likely_benign | 0.1597 | benign | -0.609 | Destabilizing | 0.999 | D | 0.563 | neutral | N | 0.479904008 | None | None | N |
| K/S | 0.925 | likely_pathogenic | 0.9479 | pathogenic | -1.2 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| K/T | 0.7495 | likely_pathogenic | 0.8135 | pathogenic | -0.856 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | N | 0.482542981 | None | None | N |
| K/V | 0.7925 | likely_pathogenic | 0.8378 | pathogenic | -0.01 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| K/W | 0.9715 | likely_pathogenic | 0.9771 | pathogenic | -0.233 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| K/Y | 0.948 | likely_pathogenic | 0.9578 | pathogenic | 0.043 | Stabilizing | 1.0 | D | 0.708 | prob.delet. | 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.