Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20215 | 60868;60869;60870 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| N2AB | 18574 | 55945;55946;55947 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| N2A | 17647 | 53164;53165;53166 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| N2B | 11150 | 33673;33674;33675 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| Novex-1 | 11275 | 34048;34049;34050 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| Novex-2 | 11342 | 34249;34250;34251 | chr2:178591082;178591081;178591080 | chr2:179455809;179455808;179455807 |
| 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 | rs1223437077  |
None | 0.024 | N | 0.348 | 0.163 | 0.269111216191 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/G | rs1223437077 |
None | 0.024 | N | 0.348 | 0.163 | 0.269111216191 | gnomAD-4.0.0 | 6.57497E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.47063E-05 | 0 | 0 |
| R/S | rs1248408963 |
0.1 | 0.012 | N | 0.369 | 0.135 | 0.165133752707 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 8.71E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/S | rs1248408963 |
0.1 | 0.012 | N | 0.369 | 0.135 | 0.165133752707 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 2.62226E-04 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 4.79386E-04 |
| R/S | rs1248408963 |
0.1 | 0.012 | N | 0.369 | 0.135 | 0.165133752707 | gnomAD-4.0.0 | 1.15371E-05 | None | None | None | None | N | None | 0 | 1.18725E-04 | None | 0 | 0 | None | 0 | 0 | 2.39428E-06 | 0 | 2.84576E-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 | 0.2615 | likely_benign | 0.2232 | benign | -0.001 | Destabilizing | 0.016 | N | 0.374 | neutral | None | None | None | None | N |
| R/C | 0.1658 | likely_benign | 0.1514 | benign | 0.072 | Stabilizing | 0.864 | D | 0.243 | neutral | None | None | None | None | N |
| R/D | 0.475 | ambiguous | 0.4412 | ambiguous | -0.037 | Destabilizing | 0.016 | N | 0.351 | neutral | None | None | None | None | N |
| R/E | 0.2427 | likely_benign | 0.2233 | benign | 0.032 | Stabilizing | 0.016 | N | 0.324 | neutral | None | None | None | None | N |
| R/F | 0.5452 | ambiguous | 0.4953 | ambiguous | -0.156 | Destabilizing | 0.628 | D | 0.288 | neutral | None | None | None | None | N |
| R/G | 0.1469 | likely_benign | 0.128 | benign | -0.222 | Destabilizing | 0.024 | N | 0.348 | neutral | N | 0.368328491 | None | None | N |
| R/H | 0.1052 | likely_benign | 0.0985 | benign | -0.785 | Destabilizing | 0.356 | N | 0.337 | neutral | None | None | None | None | N |
| R/I | 0.2614 | likely_benign | 0.2381 | benign | 0.553 | Stabilizing | 0.356 | N | 0.339 | neutral | None | None | None | None | N |
| R/K | 0.0822 | likely_benign | 0.0702 | benign | 0.008 | Stabilizing | None | N | 0.219 | neutral | N | 0.354671335 | None | None | N |
| R/L | 0.2126 | likely_benign | 0.1912 | benign | 0.553 | Stabilizing | 0.031 | N | 0.348 | neutral | None | None | None | None | N |
| R/M | 0.2011 | likely_benign | 0.1737 | benign | 0.194 | Stabilizing | 0.56 | D | 0.315 | neutral | N | 0.460126718 | None | None | N |
| R/N | 0.3819 | ambiguous | 0.3302 | benign | 0.399 | Stabilizing | None | N | 0.189 | neutral | None | None | None | None | N |
| R/P | 0.6473 | likely_pathogenic | 0.617 | pathogenic | 0.39 | Stabilizing | 0.136 | N | 0.371 | neutral | None | None | None | None | N |
| R/Q | 0.0833 | likely_benign | 0.0803 | benign | 0.251 | Stabilizing | 0.038 | N | 0.399 | neutral | None | None | None | None | N |
| R/S | 0.2749 | likely_benign | 0.2409 | benign | 0.01 | Stabilizing | 0.012 | N | 0.369 | neutral | N | 0.372294303 | None | None | N |
| R/T | 0.1362 | likely_benign | 0.1202 | benign | 0.217 | Stabilizing | 0.024 | N | 0.389 | neutral | N | 0.394901804 | None | None | N |
| R/V | 0.2998 | likely_benign | 0.2714 | benign | 0.39 | Stabilizing | 0.072 | N | 0.385 | neutral | None | None | None | None | N |
| R/W | 0.1979 | likely_benign | 0.1818 | benign | -0.155 | Destabilizing | 0.828 | D | 0.255 | neutral | N | 0.484734374 | None | None | N |
| R/Y | 0.4301 | ambiguous | 0.3785 | ambiguous | 0.241 | Stabilizing | 0.356 | N | 0.309 | 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.