Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26280 | 79063;79064;79065 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| N2AB | 24639 | 74140;74141;74142 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| N2A | 23712 | 71359;71360;71361 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| N2B | 17215 | 51868;51869;51870 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| Novex-1 | 17340 | 52243;52244;52245 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| Novex-2 | 17407 | 52444;52445;52446 | chr2:178567294;178567293;178567292 | chr2:179432021;179432020;179432019 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/H | None | None | 0.979 | D | 0.501 | 0.391 | 0.35139820857 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| N/T | rs569174612  |
-0.222 | 0.003 | N | 0.106 | 0.109 | 0.209622950755 | gnomAD-2.1.1 | 4.13E-06 | None | None | None | None | I | None | 6.54E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/T | rs569174612 |
-0.222 | 0.003 | N | 0.106 | 0.109 | 0.209622950755 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/T | rs569174612 |
-0.222 | 0.003 | N | 0.106 | 0.109 | 0.209622950755 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| N/T | rs569174612 |
-0.222 | 0.003 | N | 0.106 | 0.109 | 0.209622950755 | gnomAD-4.0.0 | 2.5842E-06 | None | None | None | None | I | None | 3.40472E-05 | 0 | None | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.1944 | likely_benign | 0.2043 | benign | -0.888 | Destabilizing | 0.373 | N | 0.473 | neutral | None | None | None | None | I |
| N/C | 0.2557 | likely_benign | 0.2185 | benign | -0.074 | Destabilizing | 0.996 | D | 0.578 | neutral | None | None | None | None | I |
| N/D | 0.2476 | likely_benign | 0.2623 | benign | -0.601 | Destabilizing | 0.684 | D | 0.374 | neutral | D | 0.532019394 | None | None | I |
| N/E | 0.4692 | ambiguous | 0.4806 | ambiguous | -0.55 | Destabilizing | 0.742 | D | 0.37 | neutral | None | None | None | None | I |
| N/F | 0.4034 | ambiguous | 0.3722 | ambiguous | -0.852 | Destabilizing | 0.953 | D | 0.609 | neutral | None | None | None | None | I |
| N/G | 0.3505 | ambiguous | 0.3561 | ambiguous | -1.172 | Destabilizing | 0.543 | D | 0.354 | neutral | None | None | None | None | I |
| N/H | 0.0975 | likely_benign | 0.0858 | benign | -0.994 | Destabilizing | 0.979 | D | 0.501 | neutral | D | 0.530115239 | None | None | I |
| N/I | 0.1413 | likely_benign | 0.1372 | benign | -0.186 | Destabilizing | 0.884 | D | 0.591 | neutral | D | 0.534963699 | None | None | I |
| N/K | 0.3474 | ambiguous | 0.3485 | ambiguous | -0.217 | Destabilizing | 0.684 | D | 0.373 | neutral | N | 0.508814461 | None | None | I |
| N/L | 0.1616 | likely_benign | 0.1667 | benign | -0.186 | Destabilizing | 0.59 | D | 0.548 | neutral | None | None | None | None | I |
| N/M | 0.2005 | likely_benign | 0.1957 | benign | 0.364 | Stabilizing | 0.996 | D | 0.571 | neutral | None | None | None | None | I |
| N/P | 0.6897 | likely_pathogenic | 0.7248 | pathogenic | -0.391 | Destabilizing | 0.953 | D | 0.579 | neutral | None | None | None | None | I |
| N/Q | 0.3216 | likely_benign | 0.3115 | benign | -0.933 | Destabilizing | 0.953 | D | 0.47 | neutral | None | None | None | None | I |
| N/R | 0.3557 | ambiguous | 0.3512 | ambiguous | -0.133 | Destabilizing | 0.742 | D | 0.46 | neutral | None | None | None | None | I |
| N/S | 0.0831 | likely_benign | 0.0888 | benign | -0.788 | Destabilizing | 0.034 | N | 0.111 | neutral | N | 0.485764243 | None | None | I |
| N/T | 0.0868 | likely_benign | 0.0921 | benign | -0.56 | Destabilizing | 0.003 | N | 0.106 | neutral | N | 0.469045351 | None | None | I |
| N/V | 0.1516 | likely_benign | 0.1481 | benign | -0.391 | Destabilizing | 0.59 | D | 0.581 | neutral | None | None | None | None | I |
| N/W | 0.7166 | likely_pathogenic | 0.6637 | pathogenic | -0.597 | Destabilizing | 0.996 | D | 0.616 | neutral | None | None | None | None | I |
| N/Y | 0.1546 | likely_benign | 0.1411 | benign | -0.395 | Destabilizing | 0.979 | D | 0.594 | neutral | N | 0.495785322 | None | None | I |
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.