Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27240 | 81943;81944;81945 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| N2AB | 25599 | 77020;77021;77022 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| N2A | 24672 | 74239;74240;74241 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| N2B | 18175 | 54748;54749;54750 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| Novex-1 | 18300 | 55123;55124;55125 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| Novex-2 | 18367 | 55324;55325;55326 | chr2:178564414;178564413;178564412 | chr2:179429141;179429140;179429139 |
| 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/I | rs1704895564  |
None | 0.379 | N | 0.519 | 0.273 | 0.33110744837 | gnomAD-4.0.0 | 4.77754E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 8.35375E-05 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1704894425 |
None | 0.016 | N | 0.285 | 0.219 | 0.151104730317 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/S | rs1704894425 |
None | 0.016 | N | 0.285 | 0.219 | 0.151104730317 | gnomAD-4.0.0 | 6.57255E-06 | None | None | None | None | N | None | 2.41196E-05 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4913 | ambiguous | 0.3781 | ambiguous | -0.949 | Destabilizing | 0.25 | N | 0.463 | neutral | None | None | None | None | N |
| R/C | 0.2352 | likely_benign | 0.1896 | benign | -0.927 | Destabilizing | 0.992 | D | 0.584 | neutral | None | None | None | None | N |
| R/D | 0.792 | likely_pathogenic | 0.7096 | pathogenic | -0.011 | Destabilizing | 0.85 | D | 0.561 | neutral | None | None | None | None | N |
| R/E | 0.43 | ambiguous | 0.3412 | ambiguous | 0.127 | Stabilizing | 0.617 | D | 0.478 | neutral | None | None | None | None | N |
| R/F | 0.7357 | likely_pathogenic | 0.6429 | pathogenic | -0.682 | Destabilizing | 0.92 | D | 0.604 | neutral | None | None | None | None | N |
| R/G | 0.4669 | ambiguous | 0.3563 | ambiguous | -1.27 | Destabilizing | 0.379 | N | 0.526 | neutral | N | 0.487811965 | None | None | N |
| R/H | 0.178 | likely_benign | 0.149 | benign | -1.432 | Destabilizing | 0.92 | D | 0.52 | neutral | None | None | None | None | N |
| R/I | 0.3521 | ambiguous | 0.253 | benign | -0.078 | Destabilizing | 0.379 | N | 0.519 | neutral | N | 0.48384894 | None | None | N |
| R/K | 0.1272 | likely_benign | 0.1103 | benign | -0.903 | Destabilizing | 0.201 | N | 0.51 | neutral | N | 0.401230344 | None | None | N |
| R/L | 0.3516 | ambiguous | 0.2757 | benign | -0.078 | Destabilizing | 0.25 | N | 0.503 | neutral | None | None | None | None | N |
| R/M | 0.3655 | ambiguous | 0.2798 | benign | -0.464 | Destabilizing | 0.92 | D | 0.578 | neutral | None | None | None | None | N |
| R/N | 0.6743 | likely_pathogenic | 0.5789 | pathogenic | -0.399 | Destabilizing | 0.447 | N | 0.517 | neutral | None | None | None | None | N |
| R/P | 0.7097 | likely_pathogenic | 0.6352 | pathogenic | -0.348 | Destabilizing | 0.92 | D | 0.589 | neutral | None | None | None | None | N |
| R/Q | 0.1267 | likely_benign | 0.1119 | benign | -0.542 | Destabilizing | 0.85 | D | 0.563 | neutral | None | None | None | None | N |
| R/S | 0.5897 | likely_pathogenic | 0.4704 | ambiguous | -1.24 | Destabilizing | 0.016 | N | 0.285 | neutral | N | 0.444925193 | None | None | N |
| R/T | 0.3011 | likely_benign | 0.226 | benign | -0.914 | Destabilizing | 0.379 | N | 0.511 | neutral | N | 0.428320944 | None | None | N |
| R/V | 0.4234 | ambiguous | 0.3246 | benign | -0.348 | Destabilizing | 0.009 | N | 0.341 | neutral | None | None | None | None | N |
| R/W | 0.3482 | ambiguous | 0.292 | benign | -0.277 | Destabilizing | 0.992 | D | 0.648 | neutral | None | None | None | None | N |
| R/Y | 0.5227 | ambiguous | 0.4436 | ambiguous | -0.018 | Destabilizing | 0.972 | D | 0.605 | 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.