Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29077 | 87454;87455;87456 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| N2AB | 27436 | 82531;82532;82533 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| N2A | 26509 | 79750;79751;79752 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| N2B | 20012 | 60259;60260;60261 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| Novex-1 | 20137 | 60634;60635;60636 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| Novex-2 | 20204 | 60835;60836;60837 | chr2:178558125;178558124;178558123 | chr2:179422852;179422851;179422850 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.704 | N | 0.495 | 0.203 | 0.271763555656 | gnomAD-4.0.0 | 1.59114E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85788E-06 | 0 | 0 |
| T/I | rs763627957  |
0.018 | 0.988 | N | 0.555 | 0.372 | 0.447311733946 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| T/I | rs763627957 |
0.018 | 0.988 | N | 0.555 | 0.372 | 0.447311733946 | gnomAD-4.0.0 | 4.78932E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39661E-06 | 0 | 1.65645E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0869 | likely_benign | 0.086 | benign | -0.583 | Destabilizing | 0.704 | D | 0.495 | neutral | N | 0.517551374 | None | None | N |
| T/C | 0.34 | ambiguous | 0.3066 | benign | -0.369 | Destabilizing | 0.999 | D | 0.559 | neutral | None | None | None | None | N |
| T/D | 0.4192 | ambiguous | 0.3799 | ambiguous | 0.343 | Stabilizing | 0.939 | D | 0.503 | neutral | None | None | None | None | N |
| T/E | 0.3428 | ambiguous | 0.3078 | benign | 0.312 | Stabilizing | 0.939 | D | 0.481 | neutral | None | None | None | None | N |
| T/F | 0.1388 | likely_benign | 0.123 | benign | -0.897 | Destabilizing | 0.991 | D | 0.608 | neutral | None | None | None | None | N |
| T/G | 0.2506 | likely_benign | 0.2344 | benign | -0.78 | Destabilizing | 0.939 | D | 0.536 | neutral | None | None | None | None | N |
| T/H | 0.2168 | likely_benign | 0.1917 | benign | -1.05 | Destabilizing | 0.1 | N | 0.46 | neutral | None | None | None | None | N |
| T/I | 0.1069 | likely_benign | 0.1037 | benign | -0.171 | Destabilizing | 0.988 | D | 0.555 | neutral | N | 0.489308767 | None | None | N |
| T/K | 0.2802 | likely_benign | 0.2578 | benign | -0.378 | Destabilizing | 0.939 | D | 0.497 | neutral | None | None | None | None | N |
| T/L | 0.0792 | likely_benign | 0.0778 | benign | -0.171 | Destabilizing | 0.969 | D | 0.487 | neutral | None | None | None | None | N |
| T/M | 0.0795 | likely_benign | 0.0802 | benign | -0.007 | Destabilizing | 0.999 | D | 0.57 | neutral | None | None | None | None | N |
| T/N | 0.1083 | likely_benign | 0.1081 | benign | -0.259 | Destabilizing | 0.92 | D | 0.471 | neutral | N | 0.507201094 | None | None | N |
| T/P | 0.5746 | likely_pathogenic | 0.5273 | ambiguous | -0.277 | Destabilizing | 0.988 | D | 0.558 | neutral | D | 0.537350643 | None | None | N |
| T/Q | 0.235 | likely_benign | 0.2174 | benign | -0.419 | Destabilizing | 0.991 | D | 0.569 | neutral | None | None | None | None | N |
| T/R | 0.2554 | likely_benign | 0.229 | benign | -0.179 | Destabilizing | 0.991 | D | 0.554 | neutral | None | None | None | None | N |
| T/S | 0.0861 | likely_benign | 0.0834 | benign | -0.558 | Destabilizing | 0.159 | N | 0.199 | neutral | N | 0.408495538 | None | None | N |
| T/V | 0.1056 | likely_benign | 0.0992 | benign | -0.277 | Destabilizing | 0.969 | D | 0.464 | neutral | None | None | None | None | N |
| T/W | 0.546 | ambiguous | 0.4784 | ambiguous | -0.85 | Destabilizing | 0.999 | D | 0.627 | neutral | None | None | None | None | N |
| T/Y | 0.2157 | likely_benign | 0.1858 | benign | -0.579 | Destabilizing | 0.982 | D | 0.603 | 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.