Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30553 | 91882;91883;91884 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| N2AB | 28912 | 86959;86960;86961 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| N2A | 27985 | 84178;84179;84180 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| N2B | 21488 | 64687;64688;64689 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| Novex-1 | 21613 | 65062;65063;65064 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| Novex-2 | 21680 | 65263;65264;65265 | chr2:178550181;178550180;178550179 | chr2:179414908;179414907;179414906 |
| 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/S | rs1257917653  |
-0.176 | 1.0 | N | 0.677 | 0.336 | 0.31291088546 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| R/S | rs1257917653 |
-0.176 | 1.0 | N | 0.677 | 0.336 | 0.31291088546 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/S | rs1257917653 |
-0.176 | 1.0 | N | 0.677 | 0.336 | 0.31291088546 | gnomAD-4.0.0 | 6.57177E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.46985E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9093 | likely_pathogenic | 0.8979 | pathogenic | 0.009 | Stabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | I |
| R/C | 0.4404 | ambiguous | 0.4184 | ambiguous | -0.311 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | I |
| R/D | 0.98 | likely_pathogenic | 0.9766 | pathogenic | -0.361 | Destabilizing | 1.0 | D | 0.716 | prob.delet. | None | None | None | None | I |
| R/E | 0.8648 | likely_pathogenic | 0.853 | pathogenic | -0.328 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | I |
| R/F | 0.8822 | likely_pathogenic | 0.874 | pathogenic | -0.34 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | None | None | None | None | I |
| R/G | 0.8575 | likely_pathogenic | 0.8384 | pathogenic | -0.111 | Destabilizing | 1.0 | D | 0.66 | neutral | N | 0.51064712 | None | None | I |
| R/H | 0.2802 | likely_benign | 0.2639 | benign | -0.593 | Destabilizing | 1.0 | D | 0.751 | deleterious | None | None | None | None | I |
| R/I | 0.6288 | likely_pathogenic | 0.6265 | pathogenic | 0.277 | Stabilizing | 1.0 | D | 0.733 | prob.delet. | D | 0.524746705 | None | None | I |
| R/K | 0.2185 | likely_benign | 0.1984 | benign | -0.237 | Destabilizing | 0.997 | D | 0.523 | neutral | N | 0.455577408 | None | None | I |
| R/L | 0.6214 | likely_pathogenic | 0.5951 | pathogenic | 0.277 | Stabilizing | 1.0 | D | 0.66 | neutral | None | None | None | None | I |
| R/M | 0.7247 | likely_pathogenic | 0.7143 | pathogenic | -0.138 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | I |
| R/N | 0.9303 | likely_pathogenic | 0.9248 | pathogenic | -0.174 | Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | I |
| R/P | 0.9874 | likely_pathogenic | 0.9851 | pathogenic | 0.204 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/Q | 0.2697 | likely_benign | 0.2579 | benign | -0.196 | Destabilizing | 1.0 | D | 0.726 | prob.delet. | None | None | None | None | I |
| R/S | 0.9058 | likely_pathogenic | 0.8998 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | N | 0.496519954 | None | None | I |
| R/T | 0.8239 | likely_pathogenic | 0.81 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.675 | neutral | N | 0.504427361 | None | None | I |
| R/V | 0.7523 | likely_pathogenic | 0.7407 | pathogenic | 0.204 | Stabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/W | 0.5497 | ambiguous | 0.5439 | ambiguous | -0.55 | Destabilizing | 1.0 | D | 0.784 | deleterious | None | None | None | None | I |
| R/Y | 0.7538 | likely_pathogenic | 0.7398 | pathogenic | -0.152 | Destabilizing | 1.0 | D | 0.741 | deleterious | None | None | None | None | I |
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.