Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28326 | 85201;85202;85203 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| N2AB | 26685 | 80278;80279;80280 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| N2A | 25758 | 77497;77498;77499 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| N2B | 19261 | 58006;58007;58008 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| Novex-1 | 19386 | 58381;58382;58383 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| Novex-2 | 19453 | 58582;58583;58584 | chr2:178561156;178561155;178561154 | chr2:179425883;179425882;179425881 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/G | rs749633038  |
-2.639 | 0.956 | D | 0.556 | 0.505 | 0.801920504441 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/G | rs749633038 |
-2.639 | 0.956 | D | 0.556 | 0.505 | 0.801920504441 | gnomAD-4.0.0 | 6.84265E-07 | None | None | None | None | N | None | 0 | 2.23624E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/P | rs200843338 |
-1.776 | 0.998 | D | 0.686 | 0.436 | 0.645427016598 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/P | rs200843338 |
-1.776 | 0.998 | D | 0.686 | 0.436 | 0.645427016598 | gnomAD-4.0.0 | 1.36851E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31873E-05 | 0 |
| R/Q | rs200843338 |
-0.976 | 0.994 | N | 0.529 | 0.423 | None | gnomAD-2.1.1 | 2.43132E-04 | None | None | None | None | N | None | 0 | 7.35544E-04 | None | 0 | 0 | None | 0 | None | 0 | 3.13288E-04 | 2.81057E-04 |
| R/Q | rs200843338 |
-0.976 | 0.994 | N | 0.529 | 0.423 | None | gnomAD-3.1.2 | 1.31496E-04 | None | None | None | None | N | None | 2.41E-05 | 5.24384E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.61722E-04 | 0 | 0 |
| R/Q | rs200843338 |
-0.976 | 0.994 | N | 0.529 | 0.423 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs200843338 |
-0.976 | 0.994 | N | 0.529 | 0.423 | None | gnomAD-4.0.0 | 2.00167E-04 | None | None | None | None | N | None | 2.6661E-05 | 7.00093E-04 | None | 0 | 0 | None | 3.12989E-05 | 0 | 2.23769E-04 | 1.09806E-05 | 1.92055E-04 |
| R/W | rs749633038 |
-0.975 | 1.0 | D | 0.717 | 0.542 | 0.714975409369 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 3.27E-05 | None | 4.66E-05 | 4.45E-05 | 0 |
| R/W | rs749633038 |
-0.975 | 1.0 | D | 0.717 | 0.542 | 0.714975409369 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs749633038 |
-0.975 | 1.0 | D | 0.717 | 0.542 | 0.714975409369 | gnomAD-4.0.0 | 2.16923E-05 | None | None | None | None | N | None | 2.6708E-05 | 0 | None | 0 | 2.23075E-05 | None | 0 | 1.64366E-04 | 2.03423E-05 | 4.39194E-05 | 4.80354E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.981 | likely_pathogenic | 0.9813 | pathogenic | -2.246 | Highly Destabilizing | 0.919 | D | 0.527 | neutral | None | None | None | None | N |
| R/C | 0.5739 | likely_pathogenic | 0.6204 | pathogenic | -1.954 | Destabilizing | 0.999 | D | 0.741 | deleterious | None | None | None | None | N |
| R/D | 0.998 | likely_pathogenic | 0.9976 | pathogenic | -1.119 | Destabilizing | 0.976 | D | 0.602 | neutral | None | None | None | None | N |
| R/E | 0.9706 | likely_pathogenic | 0.9676 | pathogenic | -0.893 | Destabilizing | 0.919 | D | 0.498 | neutral | None | None | None | None | N |
| R/F | 0.9848 | likely_pathogenic | 0.9864 | pathogenic | -1.402 | Destabilizing | 0.988 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/G | 0.9828 | likely_pathogenic | 0.981 | pathogenic | -2.576 | Highly Destabilizing | 0.956 | D | 0.556 | neutral | D | 0.561719611 | None | None | N |
| R/H | 0.3418 | ambiguous | 0.3868 | ambiguous | -2.319 | Highly Destabilizing | 0.034 | N | 0.385 | neutral | None | None | None | None | N |
| R/I | 0.9527 | likely_pathogenic | 0.9603 | pathogenic | -1.271 | Destabilizing | 0.988 | D | 0.721 | prob.delet. | None | None | None | None | N |
| R/K | 0.5291 | ambiguous | 0.5759 | pathogenic | -1.231 | Destabilizing | 0.825 | D | 0.563 | neutral | None | None | None | None | N |
| R/L | 0.9102 | likely_pathogenic | 0.9225 | pathogenic | -1.271 | Destabilizing | 0.956 | D | 0.563 | neutral | N | 0.521156235 | None | None | N |
| R/M | 0.959 | likely_pathogenic | 0.9673 | pathogenic | -1.759 | Destabilizing | 0.999 | D | 0.628 | neutral | None | None | None | None | N |
| R/N | 0.9876 | likely_pathogenic | 0.9877 | pathogenic | -1.338 | Destabilizing | 0.919 | D | 0.501 | neutral | None | None | None | None | N |
| R/P | 0.9992 | likely_pathogenic | 0.999 | pathogenic | -1.588 | Destabilizing | 0.998 | D | 0.686 | prob.neutral | D | 0.56222659 | None | None | N |
| R/Q | 0.4979 | ambiguous | 0.5228 | ambiguous | -1.183 | Destabilizing | 0.994 | D | 0.529 | neutral | N | 0.495339297 | None | None | N |
| R/S | 0.986 | likely_pathogenic | 0.9854 | pathogenic | -2.247 | Highly Destabilizing | 0.919 | D | 0.528 | neutral | None | None | None | None | N |
| R/T | 0.9732 | likely_pathogenic | 0.9742 | pathogenic | -1.811 | Destabilizing | 0.988 | D | 0.545 | neutral | None | None | None | None | N |
| R/V | 0.9582 | likely_pathogenic | 0.9635 | pathogenic | -1.588 | Destabilizing | 0.988 | D | 0.689 | prob.neutral | None | None | None | None | N |
| R/W | 0.8073 | likely_pathogenic | 0.8192 | pathogenic | -0.9 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | D | 0.550616795 | None | None | N |
| R/Y | 0.942 | likely_pathogenic | 0.9475 | pathogenic | -0.815 | Destabilizing | 0.976 | D | 0.659 | 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.