Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17923 | 53992;53993;53994 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| N2AB | 16282 | 49069;49070;49071 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| N2A | 15355 | 46288;46289;46290 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| N2B | 8858 | 26797;26798;26799 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| Novex-1 | 8983 | 27172;27173;27174 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| Novex-2 | 9050 | 27373;27374;27375 | chr2:178605528;178605527;178605526 | chr2:179470255;179470254;179470253 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/P | None | None | 0.004 | N | 0.483 | 0.297 | 0.534668972696 | gnomAD-4.0.0 | 1.59428E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 1.88267E-05 | 0 | 0 | 0 | 0 |
| L/R | rs2054576322  |
None | 0.681 | N | 0.623 | 0.221 | 0.560642594899 | gnomAD-4.0.0 | 1.11599E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.94563E-04 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1478 | likely_benign | 0.1945 | benign | -1.25 | Destabilizing | 0.25 | N | 0.446 | neutral | None | None | None | None | N |
| L/C | 0.3873 | ambiguous | 0.4471 | ambiguous | -0.879 | Destabilizing | 0.977 | D | 0.546 | neutral | None | None | None | None | N |
| L/D | 0.5395 | ambiguous | 0.6258 | pathogenic | -0.361 | Destabilizing | 0.85 | D | 0.611 | neutral | None | None | None | None | N |
| L/E | 0.2442 | likely_benign | 0.2895 | benign | -0.345 | Destabilizing | 0.617 | D | 0.574 | neutral | None | None | None | None | N |
| L/F | 0.1344 | likely_benign | 0.1663 | benign | -0.72 | Destabilizing | 0.85 | D | 0.531 | neutral | None | None | None | None | N |
| L/G | 0.4618 | ambiguous | 0.5429 | ambiguous | -1.559 | Destabilizing | 0.617 | D | 0.573 | neutral | None | None | None | None | N |
| L/H | 0.1548 | likely_benign | 0.1939 | benign | -0.597 | Destabilizing | 0.992 | D | 0.579 | neutral | None | None | None | None | N |
| L/I | 0.0697 | likely_benign | 0.0885 | benign | -0.486 | Destabilizing | 0.217 | N | 0.423 | neutral | None | None | None | None | N |
| L/K | 0.1731 | likely_benign | 0.207 | benign | -0.764 | Destabilizing | 0.021 | N | 0.452 | neutral | None | None | None | None | N |
| L/M | 0.0957 | likely_benign | 0.1017 | benign | -0.532 | Destabilizing | 0.81 | D | 0.526 | neutral | N | 0.45881721 | None | None | N |
| L/N | 0.2965 | likely_benign | 0.3302 | benign | -0.692 | Destabilizing | 0.92 | D | 0.623 | neutral | None | None | None | None | N |
| L/P | 0.2245 | likely_benign | 0.3486 | ambiguous | -0.708 | Destabilizing | 0.004 | N | 0.483 | neutral | N | 0.451525878 | None | None | N |
| L/Q | 0.1117 | likely_benign | 0.1318 | benign | -0.796 | Destabilizing | 0.81 | D | 0.631 | neutral | N | 0.431899967 | None | None | N |
| L/R | 0.1334 | likely_benign | 0.1762 | benign | -0.237 | Destabilizing | 0.681 | D | 0.623 | neutral | N | 0.411236693 | None | None | N |
| L/S | 0.1801 | likely_benign | 0.237 | benign | -1.339 | Destabilizing | 0.447 | N | 0.525 | neutral | None | None | None | None | N |
| L/T | 0.0902 | likely_benign | 0.1027 | benign | -1.196 | Destabilizing | 0.009 | N | 0.291 | neutral | None | None | None | None | N |
| L/V | 0.0646 | likely_benign | 0.0795 | benign | -0.708 | Destabilizing | 0.004 | N | 0.23 | neutral | N | 0.407580313 | None | None | N |
| L/W | 0.2696 | likely_benign | 0.3414 | ambiguous | -0.768 | Destabilizing | 0.992 | D | 0.591 | neutral | None | None | None | None | N |
| L/Y | 0.3217 | likely_benign | 0.3728 | ambiguous | -0.537 | Destabilizing | 0.92 | D | 0.578 | 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.