Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 21810 | 65653;65654;65655 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| N2AB | 20169 | 60730;60731;60732 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| N2A | 19242 | 57949;57950;57951 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| N2B | 12745 | 38458;38459;38460 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| Novex-1 | 12870 | 38833;38834;38835 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| Novex-2 | 12937 | 39034;39035;39036 | chr2:178583754;178583753;178583752 | chr2:179448481;179448480;179448479 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.055 | N | 0.444 | 0.118 | 0.0846915920261 | gnomAD-4.0.0 | 6.85079E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00114E-07 | 0 | 0 |
| A/T | rs752825084  |
-1.077 | None | N | 0.089 | 0.096 | 0.0482279557977 | gnomAD-2.1.1 | 4.07E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.99E-06 | 0 |
| A/T | rs752825084 |
-1.077 | None | N | 0.089 | 0.096 | 0.0482279557977 | gnomAD-4.0.0 | 6.85079E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 9.00114E-07 | 0 | 0 |
| A/V | rs2048304433 |
None | None | N | 0.129 | 0.049 | 0.40722173914 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/V | rs2048304433 |
None | None | N | 0.129 | 0.049 | 0.40722173914 | gnomAD-4.0.0 | 1.24088E-06 | None | None | None | None | N | None | 1.33561E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 1.6039E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3222 | likely_benign | 0.2997 | benign | -0.788 | Destabilizing | 0.356 | N | 0.421 | neutral | None | None | None | None | N |
| A/D | 0.2334 | likely_benign | 0.2238 | benign | -1.391 | Destabilizing | 0.038 | N | 0.328 | neutral | None | None | None | None | N |
| A/E | 0.2343 | likely_benign | 0.2338 | benign | -1.439 | Destabilizing | 0.029 | N | 0.371 | neutral | N | 0.438729939 | None | None | N |
| A/F | 0.2312 | likely_benign | 0.2163 | benign | -1.17 | Destabilizing | 0.214 | N | 0.475 | neutral | None | None | None | None | N |
| A/G | 0.1317 | likely_benign | 0.1181 | benign | -1.231 | Destabilizing | 0.012 | N | 0.275 | neutral | N | 0.417701306 | None | None | N |
| A/H | 0.3059 | likely_benign | 0.3017 | benign | -1.395 | Destabilizing | 0.356 | N | 0.419 | neutral | None | None | None | None | N |
| A/I | 0.1378 | likely_benign | 0.1309 | benign | -0.492 | Destabilizing | None | N | 0.191 | neutral | None | None | None | None | N |
| A/K | 0.3636 | ambiguous | 0.3589 | ambiguous | -1.299 | Destabilizing | 0.038 | N | 0.361 | neutral | None | None | None | None | N |
| A/L | 0.1101 | likely_benign | 0.1063 | benign | -0.492 | Destabilizing | 0.006 | N | 0.329 | neutral | None | None | None | None | N |
| A/M | 0.1334 | likely_benign | 0.1292 | benign | -0.262 | Destabilizing | 0.214 | N | 0.423 | neutral | None | None | None | None | N |
| A/N | 0.1336 | likely_benign | 0.1319 | benign | -0.964 | Destabilizing | None | N | 0.152 | neutral | None | None | None | None | N |
| A/P | 0.283 | likely_benign | 0.2287 | benign | -0.618 | Destabilizing | 0.055 | N | 0.444 | neutral | N | 0.461275938 | None | None | N |
| A/Q | 0.2392 | likely_benign | 0.2425 | benign | -1.162 | Destabilizing | 0.214 | N | 0.477 | neutral | None | None | None | None | N |
| A/R | 0.3763 | ambiguous | 0.3811 | ambiguous | -0.856 | Destabilizing | 0.072 | N | 0.443 | neutral | None | None | None | None | N |
| A/S | 0.0695 | likely_benign | 0.0693 | benign | -1.263 | Destabilizing | None | N | 0.125 | neutral | N | 0.379353561 | None | None | N |
| A/T | 0.062 | likely_benign | 0.0626 | benign | -1.226 | Destabilizing | None | N | 0.089 | neutral | N | 0.363309461 | None | None | N |
| A/V | 0.0867 | likely_benign | 0.0844 | benign | -0.618 | Destabilizing | None | N | 0.129 | neutral | N | 0.419856177 | None | None | N |
| A/W | 0.5918 | likely_pathogenic | 0.5731 | pathogenic | -1.511 | Destabilizing | 0.864 | D | 0.452 | neutral | None | None | None | None | N |
| A/Y | 0.3339 | likely_benign | 0.3105 | benign | -1.131 | Destabilizing | 0.356 | N | 0.457 | 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.