Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15346 | 46261;46262;46263 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| N2AB | 13705 | 41338;41339;41340 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| N2A | 12778 | 38557;38558;38559 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| N2B | 6281 | 19066;19067;19068 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| Novex-1 | 6406 | 19441;19442;19443 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| Novex-2 | 6473 | 19642;19643;19644 | chr2:178620485;178620484;178620483 | chr2:179485212;179485211;179485210 |
| 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/C | rs767343871  |
-0.064 | 1.0 | D | 0.71 | 0.407 | 0.685456958132 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 4.14E-05 | 0 | None | 0 | 5.17E-05 | None | 1.30813E-04 | None | 0 | 0 | 0 |
| R/C | rs767343871 |
-0.064 | 1.0 | D | 0.71 | 0.407 | 0.685456958132 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.07987E-04 | 0 |
| R/C | rs767343871 |
-0.064 | 1.0 | D | 0.71 | 0.407 | 0.685456958132 | gnomAD-4.0.0 | 1.05446E-05 | None | None | None | None | N | None | 2.67451E-05 | 1.67084E-05 | None | 3.38455E-05 | 2.23634E-05 | None | 0 | 0 | 1.6964E-06 | 1.09878E-04 | 0 |
| R/H | rs367996763 |
-0.959 | 1.0 | D | 0.749 | 0.453 | None | gnomAD-2.1.1 | 2.02E-05 | None | None | None | None | N | None | 1.94099E-04 | 2.91E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| R/H | rs367996763 |
-0.959 | 1.0 | D | 0.749 | 0.453 | None | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 9.66E-05 | 0 | 0 | 0 | 1.94932E-04 | None | 0 | 0 | 0 | 0 | 0 |
| R/H | rs367996763 |
-0.959 | 1.0 | D | 0.749 | 0.453 | None | gnomAD-4.0.0 | 1.36455E-05 | None | None | None | None | N | None | 1.06969E-04 | 5.0122E-05 | None | 0 | 2.23684E-05 | None | 0 | 0 | 7.63377E-06 | 1.09859E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7637 | likely_pathogenic | 0.7922 | pathogenic | -0.53 | Destabilizing | 0.999 | D | 0.597 | neutral | None | None | None | None | N |
| R/C | 0.4547 | ambiguous | 0.4823 | ambiguous | -0.415 | Destabilizing | 1.0 | D | 0.71 | prob.delet. | D | 0.638968294 | None | None | N |
| R/D | 0.835 | likely_pathogenic | 0.8532 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| R/E | 0.6686 | likely_pathogenic | 0.6848 | pathogenic | 0.108 | Stabilizing | 0.999 | D | 0.626 | neutral | None | None | None | None | N |
| R/F | 0.8745 | likely_pathogenic | 0.8961 | pathogenic | -0.467 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| R/G | 0.6001 | likely_pathogenic | 0.6415 | pathogenic | -0.827 | Destabilizing | 1.0 | D | 0.659 | neutral | D | 0.635201152 | None | None | N |
| R/H | 0.2062 | likely_benign | 0.2221 | benign | -1.253 | Destabilizing | 1.0 | D | 0.749 | deleterious | D | 0.543541968 | None | None | N |
| R/I | 0.6346 | likely_pathogenic | 0.68 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| R/K | 0.1929 | likely_benign | 0.2224 | benign | -0.552 | Destabilizing | 0.998 | D | 0.502 | neutral | None | None | None | None | N |
| R/L | 0.6133 | likely_pathogenic | 0.6537 | pathogenic | 0.254 | Stabilizing | 1.0 | D | 0.659 | neutral | D | 0.597673425 | None | None | N |
| R/M | 0.6664 | likely_pathogenic | 0.6954 | pathogenic | -0.055 | Destabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| R/N | 0.7672 | likely_pathogenic | 0.7844 | pathogenic | -0.027 | Destabilizing | 1.0 | D | 0.745 | deleterious | None | None | None | None | N |
| R/P | 0.9374 | likely_pathogenic | 0.9516 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.657 | neutral | D | 0.638244893 | None | None | N |
| R/Q | 0.2175 | likely_benign | 0.2388 | benign | -0.191 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | N |
| R/S | 0.7882 | likely_pathogenic | 0.8153 | pathogenic | -0.693 | Destabilizing | 1.0 | D | 0.729 | prob.delet. | D | 0.597522623 | None | None | N |
| R/T | 0.5193 | ambiguous | 0.554 | ambiguous | -0.408 | Destabilizing | 1.0 | D | 0.723 | prob.delet. | None | None | None | None | N |
| R/V | 0.759 | likely_pathogenic | 0.7981 | pathogenic | 0.015 | Stabilizing | 1.0 | D | 0.698 | prob.neutral | None | None | None | None | N |
| R/W | 0.4697 | ambiguous | 0.4883 | ambiguous | -0.22 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | N |
| R/Y | 0.7282 | likely_pathogenic | 0.758 | pathogenic | 0.109 | Stabilizing | 1.0 | D | 0.676 | 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.