Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27284 | 82075;82076;82077 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| N2AB | 25643 | 77152;77153;77154 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| N2A | 24716 | 74371;74372;74373 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| N2B | 18219 | 54880;54881;54882 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| Novex-1 | 18344 | 55255;55256;55257 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| Novex-2 | 18411 | 55456;55457;55458 | chr2:178564282;178564281;178564280 | chr2:179429009;179429008;179429007 |
| 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 | rs746222222  |
0.011 | 0.201 | N | 0.488 | 0.065 | 0.296679040009 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 0 | 0 |
| V/I | rs746222222 |
0.011 | 0.201 | N | 0.488 | 0.065 | 0.296679040009 | gnomAD-4.0.0 | 1.92153E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.22955E-05 | None | 0 | 0 | 2.37334E-05 | 0 | 3.20246E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1452 | likely_benign | 0.1331 | benign | -0.841 | Destabilizing | 0.007 | N | 0.175 | neutral | N | 0.449954505 | None | None | N |
| V/C | 0.5959 | likely_pathogenic | 0.6182 | pathogenic | -0.809 | Destabilizing | 0.992 | D | 0.517 | neutral | None | None | None | None | N |
| V/D | 0.3091 | likely_benign | 0.2948 | benign | -0.351 | Destabilizing | 0.896 | D | 0.585 | neutral | N | 0.443081674 | None | None | N |
| V/E | 0.2724 | likely_benign | 0.261 | benign | -0.431 | Destabilizing | 0.92 | D | 0.537 | neutral | None | None | None | None | N |
| V/F | 0.1762 | likely_benign | 0.1712 | benign | -0.843 | Destabilizing | 0.681 | D | 0.523 | neutral | N | 0.460185111 | None | None | N |
| V/G | 0.1869 | likely_benign | 0.1801 | benign | -1.036 | Destabilizing | 0.549 | D | 0.533 | neutral | N | 0.459574066 | None | None | N |
| V/H | 0.5085 | ambiguous | 0.5119 | ambiguous | -0.552 | Destabilizing | 0.992 | D | 0.583 | neutral | None | None | None | None | N |
| V/I | 0.0729 | likely_benign | 0.0708 | benign | -0.456 | Destabilizing | 0.201 | N | 0.488 | neutral | N | 0.487107384 | None | None | N |
| V/K | 0.319 | likely_benign | 0.3324 | benign | -0.716 | Destabilizing | 0.766 | D | 0.539 | neutral | None | None | None | None | N |
| V/L | 0.1483 | likely_benign | 0.1674 | benign | -0.456 | Destabilizing | 0.002 | N | 0.18 | neutral | N | 0.481912208 | None | None | N |
| V/M | 0.1041 | likely_benign | 0.0988 | benign | -0.446 | Destabilizing | 0.85 | D | 0.503 | neutral | None | None | None | None | N |
| V/N | 0.1937 | likely_benign | 0.1786 | benign | -0.475 | Destabilizing | 0.92 | D | 0.58 | neutral | None | None | None | None | N |
| V/P | 0.6519 | likely_pathogenic | 0.661 | pathogenic | -0.548 | Destabilizing | 0.92 | D | 0.545 | neutral | None | None | None | None | N |
| V/Q | 0.3075 | likely_benign | 0.3075 | benign | -0.687 | Destabilizing | 0.972 | D | 0.541 | neutral | None | None | None | None | N |
| V/R | 0.3084 | likely_benign | 0.3242 | benign | -0.2 | Destabilizing | 0.92 | D | 0.58 | neutral | None | None | None | None | N |
| V/S | 0.167 | likely_benign | 0.1523 | benign | -0.931 | Destabilizing | 0.447 | N | 0.515 | neutral | None | None | None | None | N |
| V/T | 0.1178 | likely_benign | 0.1002 | benign | -0.902 | Destabilizing | 0.021 | N | 0.223 | neutral | None | None | None | None | N |
| V/W | 0.762 | likely_pathogenic | 0.7874 | pathogenic | -0.922 | Destabilizing | 0.992 | D | 0.613 | neutral | None | None | None | None | N |
| V/Y | 0.4406 | ambiguous | 0.477 | ambiguous | -0.639 | Destabilizing | 0.92 | D | 0.513 | 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.