Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29478 | 88657;88658;88659 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| N2AB | 27837 | 83734;83735;83736 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| N2A | 26910 | 80953;80954;80955 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| N2B | 20413 | 61462;61463;61464 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| Novex-1 | 20538 | 61837;61838;61839 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| Novex-2 | 20605 | 62038;62039;62040 | chr2:178555027;178555026;178555025 | chr2:179419754;179419753;179419752 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | None | N | 0.147 | 0.112 | 0.0762999501168 | gnomAD-4.0.0 | 3.18293E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71618E-06 | 0 | 0 |
| D/N | rs1288820688  |
0.084 | None | N | 0.13 | 0.104 | 0.0920862733494 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/N | rs1288820688 |
0.084 | None | N | 0.13 | 0.104 | 0.0920862733494 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/N | rs1288820688 |
0.084 | None | N | 0.13 | 0.104 | 0.0920862733494 | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 0 | 6.5505E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| D/Y | rs1288820688 |
0.002 | 0.741 | N | 0.401 | 0.278 | 0.407767136052 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 1.14784E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| D/Y | rs1288820688 |
0.002 | 0.741 | N | 0.401 | 0.278 | 0.407767136052 | 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 |
| D/Y | rs1288820688 |
0.002 | 0.741 | N | 0.401 | 0.278 | 0.407767136052 | gnomAD-4.0.0 | 6.57402E-06 | None | None | None | None | N | None | 2.41464E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1637 | likely_benign | 0.1271 | benign | -0.254 | Destabilizing | 0.027 | N | 0.293 | neutral | N | 0.48830225 | None | None | N |
| D/C | 0.4346 | ambiguous | 0.3394 | benign | -0.185 | Destabilizing | 0.935 | D | 0.407 | neutral | None | None | None | None | N |
| D/E | 0.1251 | likely_benign | 0.1108 | benign | -0.265 | Destabilizing | 0.027 | N | 0.28 | neutral | N | 0.455131038 | None | None | N |
| D/F | 0.6071 | likely_pathogenic | 0.4845 | ambiguous | -0.082 | Destabilizing | 0.791 | D | 0.402 | neutral | None | None | None | None | N |
| D/G | 0.0657 | likely_benign | 0.0596 | benign | -0.444 | Destabilizing | None | N | 0.147 | neutral | N | 0.373890948 | None | None | N |
| D/H | 0.2024 | likely_benign | 0.1486 | benign | 0.295 | Stabilizing | 0.317 | N | 0.344 | neutral | N | 0.496191014 | None | None | N |
| D/I | 0.4404 | ambiguous | 0.319 | benign | 0.197 | Stabilizing | 0.555 | D | 0.419 | neutral | None | None | None | None | N |
| D/K | 0.2074 | likely_benign | 0.157 | benign | 0.251 | Stabilizing | 0.081 | N | 0.311 | neutral | None | None | None | None | N |
| D/L | 0.4014 | ambiguous | 0.3042 | benign | 0.197 | Stabilizing | 0.38 | N | 0.445 | neutral | None | None | None | None | N |
| D/M | 0.5584 | ambiguous | 0.443 | ambiguous | 0.152 | Stabilizing | 0.935 | D | 0.401 | neutral | None | None | None | None | N |
| D/N | 0.0747 | likely_benign | 0.0619 | benign | -0.119 | Destabilizing | None | N | 0.13 | neutral | N | 0.440508303 | None | None | N |
| D/P | 0.8325 | likely_pathogenic | 0.7299 | pathogenic | 0.068 | Stabilizing | 0.555 | D | 0.359 | neutral | None | None | None | None | N |
| D/Q | 0.2001 | likely_benign | 0.1542 | benign | -0.071 | Destabilizing | 0.38 | N | 0.306 | neutral | None | None | None | None | N |
| D/R | 0.2276 | likely_benign | 0.1733 | benign | 0.539 | Stabilizing | 0.38 | N | 0.401 | neutral | None | None | None | None | N |
| D/S | 0.0999 | likely_benign | 0.083 | benign | -0.228 | Destabilizing | 0.035 | N | 0.281 | neutral | None | None | None | None | N |
| D/T | 0.2218 | likely_benign | 0.1712 | benign | -0.072 | Destabilizing | 0.081 | N | 0.311 | neutral | None | None | None | None | N |
| D/V | 0.2974 | likely_benign | 0.2244 | benign | 0.068 | Stabilizing | 0.484 | N | 0.446 | neutral | N | 0.459619361 | None | None | N |
| D/W | 0.8216 | likely_pathogenic | 0.744 | pathogenic | 0.072 | Stabilizing | 0.935 | D | 0.451 | neutral | None | None | None | None | N |
| D/Y | 0.2252 | likely_benign | 0.1755 | benign | 0.16 | Stabilizing | 0.741 | D | 0.401 | neutral | N | 0.459365872 | 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.