Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 995 | 3208;3209;3210 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| N2AB | 995 | 3208;3209;3210 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| N2A | 995 | 3208;3209;3210 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| N2B | 949 | 3070;3071;3072 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| Novex-1 | 949 | 3070;3071;3072 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| Novex-2 | 949 | 3070;3071;3072 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
| Novex-3 | 995 | 3208;3209;3210 | chr2:178782923;178782922;178782921 | chr2:179647650;179647649;179647648 |
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/G | rs1369944497  |
0.177 | None | N | 0.087 | 0.084 | 0.0666544352282 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | I | None | 1.14811E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/G | rs1369944497 |
0.177 | None | N | 0.087 | 0.084 | 0.0666544352282 | gnomAD-3.1.2 | 2.63E-05 | None | None | None | None | I | None | 9.66E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/G | rs1369944497 |
0.177 | None | N | 0.087 | 0.084 | 0.0666544352282 | gnomAD-4.0.0 | 2.62895E-05 | None | None | None | None | I | None | 9.65624E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/N | None | None | None | N | 0.136 | 0.142 | 0.101711395817 | gnomAD-4.0.0 | 2.40064E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.625E-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 | 0.1272 | likely_benign | 0.1304 | benign | -0.185 | Destabilizing | None | N | 0.08 | neutral | None | None | None | None | I |
| S/C | 0.2436 | likely_benign | 0.2311 | benign | -0.623 | Destabilizing | 0.612 | D | 0.193 | neutral | D | 0.549396791 | None | None | I |
| S/D | 0.1494 | likely_benign | 0.1453 | benign | 0.087 | Stabilizing | None | N | 0.136 | neutral | None | None | None | None | I |
| S/E | 0.2858 | likely_benign | 0.3065 | benign | -0.003 | Destabilizing | 0.016 | N | 0.238 | neutral | None | None | None | None | I |
| S/F | 0.5607 | ambiguous | 0.5617 | ambiguous | -0.96 | Destabilizing | 0.356 | N | 0.215 | neutral | None | None | None | None | I |
| S/G | 0.071 | likely_benign | 0.0699 | benign | -0.217 | Destabilizing | None | N | 0.087 | neutral | N | 0.460361019 | None | None | I |
| S/H | 0.2367 | likely_benign | 0.2324 | benign | -0.359 | Destabilizing | 0.214 | N | 0.194 | neutral | None | None | None | None | I |
| S/I | 0.3854 | ambiguous | 0.4239 | ambiguous | -0.227 | Destabilizing | 0.171 | N | 0.284 | neutral | D | 0.565948899 | None | None | I |
| S/K | 0.3721 | ambiguous | 0.3855 | ambiguous | -0.363 | Destabilizing | 0.001 | N | 0.153 | neutral | None | None | None | None | I |
| S/L | 0.2558 | likely_benign | 0.2668 | benign | -0.227 | Destabilizing | 0.072 | N | 0.265 | neutral | None | None | None | None | I |
| S/M | 0.3251 | likely_benign | 0.334 | benign | -0.443 | Destabilizing | 0.628 | D | 0.199 | neutral | None | None | None | None | I |
| S/N | 0.0697 | likely_benign | 0.0653 | benign | -0.302 | Destabilizing | None | N | 0.136 | neutral | N | 0.469906145 | None | None | I |
| S/P | 0.5327 | ambiguous | 0.5697 | pathogenic | -0.19 | Destabilizing | 0.136 | N | 0.296 | neutral | None | None | None | None | I |
| S/Q | 0.325 | likely_benign | 0.3256 | benign | -0.446 | Destabilizing | 0.001 | N | 0.137 | neutral | None | None | None | None | I |
| S/R | 0.3344 | likely_benign | 0.3508 | ambiguous | -0.086 | Destabilizing | 0.029 | N | 0.271 | neutral | N | 0.519449109 | None | None | I |
| S/T | 0.1352 | likely_benign | 0.1384 | benign | -0.391 | Destabilizing | 0.012 | N | 0.235 | neutral | N | 0.508680061 | None | None | I |
| S/V | 0.4214 | ambiguous | 0.4414 | ambiguous | -0.19 | Destabilizing | 0.038 | N | 0.282 | neutral | None | None | None | None | I |
| S/W | 0.5374 | ambiguous | 0.5627 | ambiguous | -1.083 | Destabilizing | 0.864 | D | 0.235 | neutral | None | None | None | None | I |
| S/Y | 0.3079 | likely_benign | 0.3185 | benign | -0.745 | Destabilizing | 0.628 | D | 0.218 | 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.