Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26637 | 80134;80135;80136 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| N2AB | 24996 | 75211;75212;75213 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| N2A | 24069 | 72430;72431;72432 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| N2B | 17572 | 52939;52940;52941 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| Novex-1 | 17697 | 53314;53315;53316 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| Novex-2 | 17764 | 53515;53516;53517 | chr2:178566223;178566222;178566221 | chr2:179430950;179430949;179430948 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs375605062  |
-0.724 | 0.472 | N | 0.534 | 0.144 | None | gnomAD-2.1.1 | 2.41E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 5.33E-05 | 0 |
| V/I | rs375605062 |
-0.724 | 0.472 | N | 0.534 | 0.144 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs375605062 |
-0.724 | 0.472 | N | 0.534 | 0.144 | None | gnomAD-4.0.0 | 1.48741E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.03443E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.2455 | likely_benign | 0.2149 | benign | -1.657 | Destabilizing | 0.001 | N | 0.173 | neutral | N | 0.425028002 | None | None | N |
| V/C | 0.7697 | likely_pathogenic | 0.7073 | pathogenic | -1.274 | Destabilizing | 0.987 | D | 0.537 | neutral | None | None | None | None | N |
| V/D | 0.7963 | likely_pathogenic | 0.7425 | pathogenic | -1.382 | Destabilizing | 0.884 | D | 0.588 | neutral | N | 0.504498736 | None | None | N |
| V/E | 0.7259 | likely_pathogenic | 0.6877 | pathogenic | -1.245 | Destabilizing | 0.742 | D | 0.533 | neutral | None | None | None | None | N |
| V/F | 0.2969 | likely_benign | 0.2735 | benign | -1.027 | Destabilizing | 0.939 | D | 0.576 | neutral | N | 0.513337633 | None | None | N |
| V/G | 0.3435 | ambiguous | 0.2881 | benign | -2.115 | Highly Destabilizing | 0.309 | N | 0.515 | neutral | D | 0.524402775 | None | None | N |
| V/H | 0.8687 | likely_pathogenic | 0.8322 | pathogenic | -1.638 | Destabilizing | 0.996 | D | 0.591 | neutral | None | None | None | None | N |
| V/I | 0.0935 | likely_benign | 0.0922 | benign | -0.442 | Destabilizing | 0.472 | N | 0.534 | neutral | N | 0.490172772 | None | None | N |
| V/K | 0.8041 | likely_pathogenic | 0.7758 | pathogenic | -1.318 | Destabilizing | 0.742 | D | 0.531 | neutral | None | None | None | None | N |
| V/L | 0.3264 | likely_benign | 0.3044 | benign | -0.442 | Destabilizing | 0.309 | N | 0.512 | neutral | N | 0.503736715 | None | None | N |
| V/M | 0.2416 | likely_benign | 0.2258 | benign | -0.5 | Destabilizing | 0.984 | D | 0.534 | neutral | None | None | None | None | N |
| V/N | 0.628 | likely_pathogenic | 0.5507 | ambiguous | -1.393 | Destabilizing | 0.91 | D | 0.59 | neutral | None | None | None | None | N |
| V/P | 0.8367 | likely_pathogenic | 0.7976 | pathogenic | -0.814 | Destabilizing | 0.953 | D | 0.559 | neutral | None | None | None | None | N |
| V/Q | 0.7199 | likely_pathogenic | 0.6769 | pathogenic | -1.334 | Destabilizing | 0.953 | D | 0.575 | neutral | None | None | None | None | N |
| V/R | 0.7642 | likely_pathogenic | 0.7245 | pathogenic | -1.063 | Destabilizing | 0.91 | D | 0.601 | neutral | None | None | None | None | N |
| V/S | 0.4009 | ambiguous | 0.3427 | ambiguous | -2.067 | Highly Destabilizing | 0.037 | N | 0.338 | neutral | None | None | None | None | N |
| V/T | 0.3029 | likely_benign | 0.2713 | benign | -1.78 | Destabilizing | 0.373 | N | 0.507 | neutral | None | None | None | None | N |
| V/W | 0.9102 | likely_pathogenic | 0.8896 | pathogenic | -1.331 | Destabilizing | 0.996 | D | 0.639 | neutral | None | None | None | None | N |
| V/Y | 0.7039 | likely_pathogenic | 0.6572 | pathogenic | -0.966 | Destabilizing | 0.984 | D | 0.577 | 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.