Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23875 | 71848;71849;71850 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| N2AB | 22234 | 66925;66926;66927 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| N2A | 21307 | 64144;64145;64146 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| N2B | 14810 | 44653;44654;44655 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| Novex-1 | 14935 | 45028;45029;45030 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| Novex-2 | 15002 | 45229;45230;45231 | chr2:178574509;178574508;178574507 | chr2:179439236;179439235;179439234 |
| 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 | 0.183 | N | 0.372 | 0.09 | 0.190952846119 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| T/N | rs771783837  |
-0.806 | 0.002 | N | 0.235 | 0.075 | 0.215109475489 | gnomAD-2.1.1 | 2.82E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.23E-05 | 0 |
| T/N | rs771783837 |
-0.806 | 0.002 | N | 0.235 | 0.075 | 0.215109475489 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| T/N | rs771783837 |
-0.806 | 0.002 | N | 0.235 | 0.075 | 0.215109475489 | gnomAD-4.0.0 | 1.73538E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.37363E-05 | 0 | 0 |
| T/S | None | None | 0.101 | N | 0.43 | 0.057 | 0.168933306366 | gnomAD-4.0.0 | 6.84281E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9958E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0691 | likely_benign | 0.0699 | benign | -0.618 | Destabilizing | 0.183 | N | 0.372 | neutral | N | 0.438770011 | None | None | N |
| T/C | 0.3171 | likely_benign | 0.3433 | ambiguous | -0.38 | Destabilizing | 0.983 | D | 0.563 | neutral | None | None | None | None | N |
| T/D | 0.4337 | ambiguous | 0.4546 | ambiguous | -0.246 | Destabilizing | 0.264 | N | 0.502 | neutral | None | None | None | None | N |
| T/E | 0.297 | likely_benign | 0.3036 | benign | -0.289 | Destabilizing | 0.264 | N | 0.528 | neutral | None | None | None | None | N |
| T/F | 0.2503 | likely_benign | 0.2515 | benign | -0.838 | Destabilizing | 0.557 | D | 0.615 | neutral | None | None | None | None | N |
| T/G | 0.2416 | likely_benign | 0.2532 | benign | -0.825 | Destabilizing | 0.264 | N | 0.547 | neutral | None | None | None | None | N |
| T/H | 0.2242 | likely_benign | 0.2391 | benign | -1.125 | Destabilizing | 0.836 | D | 0.611 | neutral | None | None | None | None | N |
| T/I | 0.1185 | likely_benign | 0.1263 | benign | -0.174 | Destabilizing | 0.213 | N | 0.498 | neutral | N | 0.433884267 | None | None | N |
| T/K | 0.1721 | likely_benign | 0.1842 | benign | -0.692 | Destabilizing | 0.002 | N | 0.249 | neutral | None | None | None | None | N |
| T/L | 0.0786 | likely_benign | 0.0827 | benign | -0.174 | Destabilizing | 0.001 | N | 0.213 | neutral | None | None | None | None | N |
| T/M | 0.0742 | likely_benign | 0.0736 | benign | 0.142 | Stabilizing | 0.716 | D | 0.589 | neutral | None | None | None | None | N |
| T/N | 0.1029 | likely_benign | 0.1105 | benign | -0.518 | Destabilizing | 0.002 | N | 0.235 | neutral | N | 0.450352442 | None | None | N |
| T/P | 0.0706 | likely_benign | 0.0741 | benign | -0.291 | Destabilizing | 0.794 | D | 0.606 | neutral | N | 0.416125225 | None | None | N |
| T/Q | 0.1885 | likely_benign | 0.1951 | benign | -0.77 | Destabilizing | 0.418 | N | 0.596 | neutral | None | None | None | None | N |
| T/R | 0.1489 | likely_benign | 0.1559 | benign | -0.36 | Destabilizing | 0.001 | N | 0.217 | neutral | None | None | None | None | N |
| T/S | 0.1165 | likely_benign | 0.1221 | benign | -0.75 | Destabilizing | 0.101 | N | 0.43 | neutral | N | 0.446618703 | None | None | N |
| T/V | 0.0915 | likely_benign | 0.0944 | benign | -0.291 | Destabilizing | 0.129 | N | 0.4 | neutral | None | None | None | None | N |
| T/W | 0.5695 | likely_pathogenic | 0.5722 | pathogenic | -0.777 | Destabilizing | 0.983 | D | 0.628 | neutral | None | None | None | None | N |
| T/Y | 0.2436 | likely_benign | 0.2474 | benign | -0.548 | Destabilizing | 0.836 | D | 0.619 | 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.