Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23297 | 70114;70115;70116 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| N2AB | 21656 | 65191;65192;65193 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| N2A | 20729 | 62410;62411;62412 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| N2B | 14232 | 42919;42920;42921 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| Novex-1 | 14357 | 43294;43295;43296 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| Novex-2 | 14424 | 43495;43496;43497 | chr2:178576243;178576242;178576241 | chr2:179440970;179440969;179440968 |
| 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 | rs779474257  |
-0.244 | 0.822 | N | 0.467 | 0.291 | 0.355450299083 | gnomAD-2.1.1 | 4.05E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.98E-06 | 0 |
| R/G | rs779474257 |
-0.244 | 0.822 | N | 0.467 | 0.291 | 0.355450299083 | gnomAD-4.0.0 | 2.05418E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69949E-06 | 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 | 0.6127 | likely_pathogenic | 0.6044 | pathogenic | -0.029 | Destabilizing | 0.754 | D | 0.503 | neutral | None | None | None | None | I |
| R/C | 0.2693 | likely_benign | 0.2613 | benign | -0.238 | Destabilizing | 0.998 | D | 0.616 | neutral | None | None | None | None | I |
| R/D | 0.8257 | likely_pathogenic | 0.8178 | pathogenic | -0.104 | Destabilizing | 0.956 | D | 0.503 | neutral | None | None | None | None | I |
| R/E | 0.5863 | likely_pathogenic | 0.5748 | pathogenic | -0.054 | Destabilizing | 0.754 | D | 0.509 | neutral | None | None | None | None | I |
| R/F | 0.7565 | likely_pathogenic | 0.7447 | pathogenic | -0.305 | Destabilizing | 0.993 | D | 0.593 | neutral | None | None | None | None | I |
| R/G | 0.4401 | ambiguous | 0.4372 | ambiguous | -0.196 | Destabilizing | 0.822 | D | 0.467 | neutral | N | 0.489823268 | None | None | I |
| R/H | 0.1498 | likely_benign | 0.1542 | benign | -0.621 | Destabilizing | 0.978 | D | 0.562 | neutral | None | None | None | None | I |
| R/I | 0.4842 | ambiguous | 0.4974 | ambiguous | 0.369 | Stabilizing | 0.97 | D | 0.593 | neutral | N | 0.486778739 | None | None | I |
| R/K | 0.1408 | likely_benign | 0.1523 | benign | -0.117 | Destabilizing | 0.006 | N | 0.177 | neutral | N | 0.442509324 | None | None | I |
| R/L | 0.3885 | ambiguous | 0.3817 | ambiguous | 0.369 | Stabilizing | 0.86 | D | 0.467 | neutral | None | None | None | None | I |
| R/M | 0.435 | ambiguous | 0.4614 | ambiguous | -0.022 | Destabilizing | 0.998 | D | 0.561 | neutral | None | None | None | None | I |
| R/N | 0.7206 | likely_pathogenic | 0.7151 | pathogenic | 0.068 | Stabilizing | 0.956 | D | 0.507 | neutral | None | None | None | None | I |
| R/P | 0.6182 | likely_pathogenic | 0.6142 | pathogenic | 0.255 | Stabilizing | 0.978 | D | 0.568 | neutral | None | None | None | None | I |
| R/Q | 0.1514 | likely_benign | 0.1547 | benign | -0.031 | Destabilizing | 0.956 | D | 0.529 | neutral | None | None | None | None | I |
| R/S | 0.7053 | likely_pathogenic | 0.7059 | pathogenic | -0.262 | Destabilizing | 0.822 | D | 0.515 | neutral | N | 0.478816841 | None | None | I |
| R/T | 0.4452 | ambiguous | 0.4522 | ambiguous | -0.089 | Destabilizing | 0.822 | D | 0.499 | neutral | N | 0.472602944 | None | None | I |
| R/V | 0.5466 | ambiguous | 0.5497 | ambiguous | 0.255 | Stabilizing | 0.956 | D | 0.585 | neutral | None | None | None | None | I |
| R/W | 0.2988 | likely_benign | 0.2854 | benign | -0.391 | Destabilizing | 0.998 | D | 0.652 | neutral | None | None | None | None | I |
| R/Y | 0.5684 | likely_pathogenic | 0.5523 | ambiguous | 0.019 | Stabilizing | 0.993 | D | 0.567 | neutral | 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.