Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14219 | 42880;42881;42882 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| N2AB | 12578 | 37957;37958;37959 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| N2A | 11651 | 35176;35177;35178 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| N2B | 5154 | 15685;15686;15687 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| Novex-1 | 5279 | 16060;16061;16062 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| Novex-2 | 5346 | 16261;16262;16263 | chr2:178633844;178633843;178633842 | chr2:179498571;179498570;179498569 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/N | rs748928207  |
0.031 | None | N | 0.241 | 0.034 | 0.0611884634855 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/N | rs748928207 |
0.031 | None | N | 0.241 | 0.034 | 0.0611884634855 | 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 |
| S/N | rs748928207 |
0.031 | None | N | 0.241 | 0.034 | 0.0611884634855 | gnomAD-4.0.0 | 3.09942E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23873E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0968 | likely_benign | 0.0986 | benign | -0.697 | Destabilizing | 0.055 | N | 0.384 | neutral | None | None | None | None | N |
| S/C | 0.0841 | likely_benign | 0.0957 | benign | -0.419 | Destabilizing | 0.946 | D | 0.539 | neutral | N | 0.453237379 | None | None | N |
| S/D | 0.2495 | likely_benign | 0.2597 | benign | 0.531 | Stabilizing | 0.055 | N | 0.481 | neutral | None | None | None | None | N |
| S/E | 0.2703 | likely_benign | 0.3327 | benign | 0.492 | Stabilizing | 0.055 | N | 0.485 | neutral | None | None | None | None | N |
| S/F | 0.1278 | likely_benign | 0.1588 | benign | -1.068 | Destabilizing | 0.497 | N | 0.632 | neutral | None | None | None | None | N |
| S/G | 0.1278 | likely_benign | 0.1193 | benign | -0.883 | Destabilizing | 0.042 | N | 0.453 | neutral | N | 0.496692336 | None | None | N |
| S/H | 0.1125 | likely_benign | 0.1383 | benign | -1.25 | Destabilizing | 0.002 | N | 0.368 | neutral | None | None | None | None | N |
| S/I | 0.108 | likely_benign | 0.1075 | benign | -0.322 | Destabilizing | 0.427 | N | 0.649 | neutral | N | 0.461718469 | None | None | N |
| S/K | 0.3524 | ambiguous | 0.3317 | benign | -0.386 | Destabilizing | 0.001 | N | 0.267 | neutral | None | None | None | None | N |
| S/L | 0.1159 | likely_benign | 0.1252 | benign | -0.322 | Destabilizing | 0.124 | N | 0.639 | neutral | None | None | None | None | N |
| S/M | 0.1871 | likely_benign | 0.1918 | benign | -0.131 | Destabilizing | 0.667 | D | 0.567 | neutral | None | None | None | None | N |
| S/N | 0.0858 | likely_benign | 0.0859 | benign | -0.229 | Destabilizing | None | N | 0.241 | neutral | N | 0.46079262 | None | None | N |
| S/P | 0.4505 | ambiguous | 0.571 | pathogenic | -0.416 | Destabilizing | None | N | 0.325 | neutral | None | None | None | None | N |
| S/Q | 0.2267 | likely_benign | 0.2642 | benign | -0.391 | Destabilizing | 0.22 | N | 0.538 | neutral | None | None | None | None | N |
| S/R | 0.2807 | likely_benign | 0.2839 | benign | -0.268 | Destabilizing | 0.096 | N | 0.561 | neutral | N | 0.457557164 | None | None | N |
| S/T | 0.067 | likely_benign | 0.0687 | benign | -0.386 | Destabilizing | 0.001 | N | 0.253 | neutral | N | 0.421773571 | None | None | N |
| S/V | 0.1279 | likely_benign | 0.1394 | benign | -0.416 | Destabilizing | 0.124 | N | 0.637 | neutral | None | None | None | None | N |
| S/W | 0.2297 | likely_benign | 0.297 | benign | -0.999 | Destabilizing | 0.958 | D | 0.637 | neutral | None | None | None | None | N |
| S/Y | 0.0984 | likely_benign | 0.1242 | benign | -0.737 | Destabilizing | 0.331 | N | 0.645 | 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.