Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15136 | 45631;45632;45633 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| N2AB | 13495 | 40708;40709;40710 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| N2A | 12568 | 37927;37928;37929 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| N2B | 6071 | 18436;18437;18438 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| Novex-1 | 6196 | 18811;18812;18813 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| Novex-2 | 6263 | 19012;19013;19014 | chr2:178621312;178621311;178621310 | chr2:179486039;179486038;179486037 |
| 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/N | rs72677225  |
-0.02 | 0.98 | N | 0.41 | 0.18 | 0.18274738541 | gnomAD-2.1.1 | 5.05756E-03 | None | None | None | None | N | None | 1.36861E-03 | 2.11103E-03 | None | 3.01146E-03 | 0 | None | 1.70704E-03 | None | 8.03277E-03 | 7.69595E-03 | 5.54135E-03 |
| K/N | rs72677225 |
-0.02 | 0.98 | N | 0.41 | 0.18 | 0.18274738541 | gnomAD-3.1.2 | 5.01086E-03 | None | None | None | None | N | None | 1.35253E-03 | 1.57584E-03 | 0 | 2.30548E-03 | 0 | None | 6.97718E-03 | 6.32911E-03 | 8.43913E-03 | 2.48859E-03 | 5.74163E-03 |
| K/N | rs72677225 |
-0.02 | 0.98 | N | 0.41 | 0.18 | 0.18274738541 | 1000 genomes | 2.19649E-03 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 8E-03 | None | None | None | 2E-03 | None |
| K/N | rs72677225 |
-0.02 | 0.98 | N | 0.41 | 0.18 | 0.18274738541 | gnomAD-4.0.0 | 6.65913E-03 | None | None | None | None | N | None | 1.18816E-03 | 2.09072E-03 | None | 2.50372E-03 | 0 | None | 6.85532E-03 | 3.30688E-03 | 8.03316E-03 | 1.79231E-03 | 5.67726E-03 |
| K/T | None | None | 0.4 | N | 0.277 | 0.158 | 0.199424873507 | gnomAD-4.0.0 | 3.19065E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72715E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.459 | ambiguous | 0.4138 | ambiguous | -0.107 | Destabilizing | 0.931 | D | 0.487 | neutral | None | None | None | None | N |
| K/C | 0.8851 | likely_pathogenic | 0.8568 | pathogenic | -0.297 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| K/D | 0.7079 | likely_pathogenic | 0.6821 | pathogenic | 0.172 | Stabilizing | 0.996 | D | 0.486 | neutral | None | None | None | None | N |
| K/E | 0.2622 | likely_benign | 0.2525 | benign | 0.227 | Stabilizing | 0.98 | D | 0.405 | neutral | N | 0.447945145 | None | None | N |
| K/F | 0.9032 | likely_pathogenic | 0.8871 | pathogenic | -0.068 | Destabilizing | 0.999 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/G | 0.6813 | likely_pathogenic | 0.6265 | pathogenic | -0.381 | Destabilizing | 0.985 | D | 0.506 | neutral | None | None | None | None | N |
| K/H | 0.5033 | ambiguous | 0.4635 | ambiguous | -0.63 | Destabilizing | 1.0 | D | 0.56 | neutral | None | None | None | None | N |
| K/I | 0.4806 | ambiguous | 0.4573 | ambiguous | 0.559 | Stabilizing | 0.996 | D | 0.691 | prob.neutral | None | None | None | None | N |
| K/L | 0.5172 | ambiguous | 0.4766 | ambiguous | 0.559 | Stabilizing | 0.985 | D | 0.503 | neutral | None | None | None | None | N |
| K/M | 0.3009 | likely_benign | 0.2873 | benign | 0.243 | Stabilizing | 1.0 | D | 0.563 | neutral | N | 0.448530917 | None | None | N |
| K/N | 0.5008 | ambiguous | 0.4689 | ambiguous | 0.051 | Stabilizing | 0.98 | D | 0.41 | neutral | N | 0.445636255 | None | None | N |
| K/P | 0.7072 | likely_pathogenic | 0.6488 | pathogenic | 0.367 | Stabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | N |
| K/Q | 0.1948 | likely_benign | 0.1803 | benign | -0.046 | Destabilizing | 0.997 | D | 0.465 | neutral | N | 0.438733631 | None | None | N |
| K/R | 0.1129 | likely_benign | 0.1082 | benign | -0.189 | Destabilizing | 0.99 | D | 0.419 | neutral | N | 0.446293857 | None | None | N |
| K/S | 0.5654 | likely_pathogenic | 0.5233 | ambiguous | -0.5 | Destabilizing | 0.719 | D | 0.229 | neutral | None | None | None | None | N |
| K/T | 0.2021 | likely_benign | 0.1943 | benign | -0.268 | Destabilizing | 0.4 | N | 0.277 | neutral | N | 0.423057594 | None | None | N |
| K/V | 0.4382 | ambiguous | 0.4166 | ambiguous | 0.367 | Stabilizing | 0.996 | D | 0.517 | neutral | None | None | None | None | N |
| K/W | 0.9057 | likely_pathogenic | 0.8851 | pathogenic | -0.041 | Destabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| K/Y | 0.8064 | likely_pathogenic | 0.7802 | pathogenic | 0.285 | Stabilizing | 0.999 | D | 0.68 | prob.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.