Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32795 | 98608;98609;98610 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| N2AB | 31154 | 93685;93686;93687 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| N2A | 30227 | 90904;90905;90906 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| N2B | 23730 | 71413;71414;71415 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| Novex-1 | 23855 | 71788;71789;71790 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| Novex-2 | 23922 | 71989;71990;71991 | chr2:178539682;178539681;178539680 | chr2:179404409;179404408;179404407 |
| 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/R | rs373396567  |
0.113 | None | N | 0.077 | 0.127 | 0.0551355673512 | gnomAD-2.1.1 | 6.8E-05 | None | None | None | None | I | None | 6.61978E-04 | 5.66E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 1.40568E-04 |
| S/R | rs373396567 |
0.113 | None | N | 0.077 | 0.127 | 0.0551355673512 | gnomAD-3.1.2 | 1.64569E-04 | None | None | None | None | I | None | 5.80608E-04 | 6.56E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/R | rs373396567 |
0.113 | None | N | 0.077 | 0.127 | 0.0551355673512 | gnomAD-4.0.0 | 3.0991E-05 | None | None | None | None | I | None | 5.8822E-04 | 6.67089E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.20174E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0764 | likely_benign | 0.0752 | benign | -0.603 | Destabilizing | 0.003 | N | 0.148 | neutral | None | None | None | None | I |
| S/C | 0.0785 | likely_benign | 0.0734 | benign | -0.331 | Destabilizing | 0.371 | N | 0.322 | neutral | N | 0.438969507 | None | None | I |
| S/D | 0.5278 | ambiguous | 0.494 | ambiguous | -0.31 | Destabilizing | 0.007 | N | 0.153 | neutral | None | None | None | None | I |
| S/E | 0.4771 | ambiguous | 0.4812 | ambiguous | -0.409 | Destabilizing | 0.007 | N | 0.181 | neutral | None | None | None | None | I |
| S/F | 0.2108 | likely_benign | 0.1907 | benign | -1.298 | Destabilizing | 0.112 | N | 0.524 | neutral | None | None | None | None | I |
| S/G | 0.1322 | likely_benign | 0.1251 | benign | -0.685 | Destabilizing | 0.006 | N | 0.147 | neutral | N | 0.457035193 | None | None | I |
| S/H | 0.2812 | likely_benign | 0.2604 | benign | -1.296 | Destabilizing | 0.112 | N | 0.325 | neutral | None | None | None | None | I |
| S/I | 0.0912 | likely_benign | 0.0974 | benign | -0.505 | Destabilizing | None | N | 0.304 | neutral | N | 0.400488477 | None | None | I |
| S/K | 0.4321 | ambiguous | 0.4234 | ambiguous | -0.503 | Destabilizing | 0.007 | N | 0.149 | neutral | None | None | None | None | I |
| S/L | 0.0927 | likely_benign | 0.0904 | benign | -0.505 | Destabilizing | 0.007 | N | 0.385 | neutral | None | None | None | None | I |
| S/M | 0.1488 | likely_benign | 0.155 | benign | 0.04 | Stabilizing | 0.112 | N | 0.307 | neutral | None | None | None | None | I |
| S/N | 0.1286 | likely_benign | 0.1162 | benign | -0.265 | Destabilizing | None | N | 0.085 | neutral | N | 0.457208551 | None | None | I |
| S/P | 0.1105 | likely_benign | 0.105 | benign | -0.513 | Destabilizing | 0.068 | N | 0.361 | neutral | None | None | None | None | I |
| S/Q | 0.3168 | likely_benign | 0.3168 | benign | -0.648 | Destabilizing | 0.035 | N | 0.139 | neutral | None | None | None | None | I |
| S/R | 0.3849 | ambiguous | 0.2775 | benign | -0.241 | Destabilizing | None | N | 0.077 | neutral | N | 0.307866318 | None | None | I |
| S/T | 0.0903 | likely_benign | 0.0887 | benign | -0.372 | Destabilizing | None | N | 0.05 | neutral | N | 0.387559252 | None | None | I |
| S/V | 0.1095 | likely_benign | 0.115 | benign | -0.513 | Destabilizing | 0.003 | N | 0.297 | neutral | None | None | None | None | I |
| S/W | 0.3939 | ambiguous | 0.3805 | ambiguous | -1.245 | Destabilizing | 0.747 | D | 0.388 | neutral | None | None | None | None | I |
| S/Y | 0.1871 | likely_benign | 0.1682 | benign | -0.979 | Destabilizing | 0.439 | N | 0.518 | 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.