Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27658 | 83197;83198;83199 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| N2AB | 26017 | 78274;78275;78276 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| N2A | 25090 | 75493;75494;75495 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| N2B | 18593 | 56002;56003;56004 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| Novex-1 | 18718 | 56377;56378;56379 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| Novex-2 | 18785 | 56578;56579;56580 | chr2:178563160;178563159;178563158 | chr2:179427887;179427886;179427885 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/T | rs150150605  |
-1.189 | 0.698 | N | 0.591 | 0.192 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | N | None | 2.06629E-04 | 8.48E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| A/T | rs150150605 |
-1.189 | 0.698 | N | 0.591 | 0.192 | None | gnomAD-3.1.2 | 9.86E-05 | None | None | None | None | N | None | 3.62126E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| A/T | rs150150605 |
-1.189 | 0.698 | N | 0.591 | 0.192 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| A/T | rs150150605 |
-1.189 | 0.698 | N | 0.591 | 0.192 | None | gnomAD-4.0.0 | 1.92102E-05 | None | None | None | None | N | None | 3.5999E-04 | 6.66778E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.4955 | ambiguous | 0.4914 | ambiguous | -1.129 | Destabilizing | 0.998 | D | 0.677 | prob.neutral | None | None | None | None | N |
| A/D | 0.8094 | likely_pathogenic | 0.7419 | pathogenic | -2.393 | Highly Destabilizing | 0.956 | D | 0.671 | neutral | None | None | None | None | N |
| A/E | 0.7404 | likely_pathogenic | 0.6579 | pathogenic | -2.351 | Highly Destabilizing | 0.822 | D | 0.673 | neutral | N | 0.484745644 | None | None | N |
| A/F | 0.6434 | likely_pathogenic | 0.5791 | pathogenic | -1.075 | Destabilizing | 0.978 | D | 0.723 | prob.delet. | None | None | None | None | N |
| A/G | 0.2607 | likely_benign | 0.2149 | benign | -1.532 | Destabilizing | 0.698 | D | 0.581 | neutral | N | 0.519265449 | None | None | N |
| A/H | 0.8266 | likely_pathogenic | 0.7881 | pathogenic | -1.863 | Destabilizing | 0.998 | D | 0.724 | prob.delet. | None | None | None | None | N |
| A/I | 0.4173 | ambiguous | 0.3563 | ambiguous | -0.44 | Destabilizing | 0.754 | D | 0.579 | neutral | None | None | None | None | N |
| A/K | 0.889 | likely_pathogenic | 0.8424 | pathogenic | -1.57 | Destabilizing | 0.956 | D | 0.68 | prob.neutral | None | None | None | None | N |
| A/L | 0.4078 | ambiguous | 0.3525 | ambiguous | -0.44 | Destabilizing | 0.559 | D | 0.58 | neutral | None | None | None | None | N |
| A/M | 0.3988 | ambiguous | 0.3472 | ambiguous | -0.383 | Destabilizing | 0.978 | D | 0.709 | prob.delet. | None | None | None | None | N |
| A/N | 0.6421 | likely_pathogenic | 0.583 | pathogenic | -1.479 | Destabilizing | 0.956 | D | 0.708 | prob.delet. | None | None | None | None | N |
| A/P | 0.9551 | likely_pathogenic | 0.9431 | pathogenic | -0.658 | Destabilizing | 0.97 | D | 0.703 | prob.neutral | N | 0.484999134 | None | None | N |
| A/Q | 0.6859 | likely_pathogenic | 0.625 | pathogenic | -1.558 | Destabilizing | 0.956 | D | 0.712 | prob.delet. | None | None | None | None | N |
| A/R | 0.8186 | likely_pathogenic | 0.7586 | pathogenic | -1.287 | Destabilizing | 0.956 | D | 0.703 | prob.neutral | None | None | None | None | N |
| A/S | 0.1235 | likely_benign | 0.1173 | benign | -1.747 | Destabilizing | 0.058 | N | 0.496 | neutral | N | 0.379166268 | None | None | N |
| A/T | 0.1372 | likely_benign | 0.1241 | benign | -1.626 | Destabilizing | 0.698 | D | 0.591 | neutral | N | 0.467069008 | None | None | N |
| A/V | 0.1882 | likely_benign | 0.1511 | benign | -0.658 | Destabilizing | 0.025 | N | 0.345 | neutral | N | 0.454427323 | None | None | N |
| A/W | 0.9457 | likely_pathogenic | 0.9309 | pathogenic | -1.632 | Destabilizing | 0.998 | D | 0.749 | deleterious | None | None | None | None | N |
| A/Y | 0.8136 | likely_pathogenic | 0.7798 | pathogenic | -1.212 | Destabilizing | 0.993 | D | 0.734 | prob.delet. | 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.