Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25400 | 76423;76424;76425 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| N2AB | 23759 | 71500;71501;71502 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| N2A | 22832 | 68719;68720;68721 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| N2B | 16335 | 49228;49229;49230 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| Novex-1 | 16460 | 49603;49604;49605 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| Novex-2 | 16527 | 49804;49805;49806 | chr2:178569934;178569933;178569932 | chr2:179434661;179434660;179434659 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/R | rs1575727915  |
None | 0.001 | N | 0.231 | 0.319 | 0.40218521252 | gnomAD-4.0.0 | 1.59287E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86077E-06 | 0 | 0 |
| C/S | rs397517704 |
-0.534 | 0.003 | N | 0.154 | 0.304 | 0.350307294319 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| C/S | rs397517704 |
-0.534 | 0.003 | N | 0.154 | 0.304 | 0.350307294319 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| C/S | rs397517704 |
-0.534 | 0.003 | N | 0.154 | 0.304 | 0.350307294319 | gnomAD-4.0.0 | 1.05401E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3566E-05 | 0 | 1.60226E-05 |
| C/W | None | None | 0.973 | N | 0.527 | 0.286 | 0.277317399466 | gnomAD-4.0.0 | 6.37135E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.14429E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| C/A | 0.2041 | likely_benign | 0.194 | benign | -1.186 | Destabilizing | 0.003 | N | 0.071 | neutral | None | None | None | None | N |
| C/D | 0.4538 | ambiguous | 0.416 | ambiguous | -0.876 | Destabilizing | 0.229 | N | 0.438 | neutral | None | None | None | None | N |
| C/E | 0.4641 | ambiguous | 0.4194 | ambiguous | -0.825 | Destabilizing | 0.372 | N | 0.442 | neutral | None | None | None | None | N |
| C/F | 0.124 | likely_benign | 0.1241 | benign | -0.934 | Destabilizing | 0.61 | D | 0.639 | neutral | N | 0.476620067 | None | None | N |
| C/G | 0.1283 | likely_benign | 0.1231 | benign | -1.429 | Destabilizing | 0.085 | N | 0.353 | neutral | N | 0.444490836 | None | None | N |
| C/H | 0.2375 | likely_benign | 0.222 | benign | -1.739 | Destabilizing | 0.808 | D | 0.551 | neutral | None | None | None | None | N |
| C/I | 0.2515 | likely_benign | 0.2488 | benign | -0.599 | Destabilizing | 0.109 | N | 0.314 | neutral | None | None | None | None | N |
| C/K | 0.3783 | ambiguous | 0.3423 | ambiguous | -0.83 | Destabilizing | 0.109 | N | 0.323 | neutral | None | None | None | None | N |
| C/L | 0.2647 | likely_benign | 0.2658 | benign | -0.599 | Destabilizing | None | N | 0.169 | neutral | None | None | None | None | N |
| C/M | 0.3688 | ambiguous | 0.3615 | ambiguous | 0.103 | Stabilizing | 0.675 | D | 0.387 | neutral | None | None | None | None | N |
| C/N | 0.2714 | likely_benign | 0.2598 | benign | -0.75 | Destabilizing | 0.008 | N | 0.235 | neutral | None | None | None | None | N |
| C/P | 0.9613 | likely_pathogenic | 0.9598 | pathogenic | -0.769 | Destabilizing | 0.546 | D | 0.574 | neutral | None | None | None | None | N |
| C/Q | 0.2518 | likely_benign | 0.2216 | benign | -0.831 | Destabilizing | 0.372 | N | 0.581 | neutral | None | None | None | None | N |
| C/R | 0.1461 | likely_benign | 0.1275 | benign | -0.639 | Destabilizing | 0.001 | N | 0.231 | neutral | N | 0.424326208 | None | None | N |
| C/S | 0.1286 | likely_benign | 0.1249 | benign | -1.107 | Destabilizing | 0.003 | N | 0.154 | neutral | N | 0.461516372 | None | None | N |
| C/T | 0.2256 | likely_benign | 0.2139 | benign | -0.915 | Destabilizing | 0.109 | N | 0.303 | neutral | None | None | None | None | N |
| C/V | 0.2298 | likely_benign | 0.2173 | benign | -0.769 | Destabilizing | 0.109 | N | 0.305 | neutral | None | None | None | None | N |
| C/W | 0.3358 | likely_benign | 0.3225 | benign | -1.027 | Destabilizing | 0.973 | D | 0.527 | neutral | N | 0.477380535 | None | None | N |
| C/Y | 0.1747 | likely_benign | 0.1806 | benign | -0.892 | Destabilizing | 0.906 | D | 0.623 | neutral | N | 0.490993917 | 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.