Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17645 | 53158;53159;53160 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| N2AB | 16004 | 48235;48236;48237 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| N2A | 15077 | 45454;45455;45456 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| N2B | 8580 | 25963;25964;25965 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| Novex-1 | 8705 | 26338;26339;26340 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| Novex-2 | 8772 | 26539;26540;26541 | chr2:178607854;178607853;178607852 | chr2:179472581;179472580;179472579 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/R | rs763695128  |
-0.748 | 0.055 | N | 0.721 | 0.199 | 0.17258766438 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| S/R | rs763695128 |
-0.748 | 0.055 | N | 0.721 | 0.199 | 0.17258766438 | gnomAD-4.0.0 | 2.73797E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59901E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0897 | likely_benign | 0.0853 | benign | -1.255 | Destabilizing | 0.007 | N | 0.452 | neutral | None | None | None | None | N |
| S/C | 0.07 | likely_benign | 0.0701 | benign | -1.083 | Destabilizing | 0.295 | N | 0.698 | prob.neutral | N | 0.505397648 | None | None | N |
| S/D | 0.6876 | likely_pathogenic | 0.6336 | pathogenic | -2.03 | Highly Destabilizing | 0.072 | N | 0.625 | neutral | None | None | None | None | N |
| S/E | 0.6303 | likely_pathogenic | 0.5858 | pathogenic | -1.818 | Destabilizing | 0.072 | N | 0.591 | neutral | None | None | None | None | N |
| S/F | 0.1841 | likely_benign | 0.1597 | benign | -0.82 | Destabilizing | 0.072 | N | 0.725 | prob.delet. | None | None | None | None | N |
| S/G | 0.1575 | likely_benign | 0.1441 | benign | -1.616 | Destabilizing | 0.024 | N | 0.565 | neutral | N | 0.489966792 | None | None | N |
| S/H | 0.2744 | likely_benign | 0.2513 | benign | -1.747 | Destabilizing | 0.628 | D | 0.696 | prob.neutral | None | None | None | None | N |
| S/I | 0.1288 | likely_benign | 0.1295 | benign | -0.325 | Destabilizing | None | N | 0.453 | neutral | N | 0.456142264 | None | None | N |
| S/K | 0.4809 | ambiguous | 0.4279 | ambiguous | -0.671 | Destabilizing | 0.072 | N | 0.597 | neutral | None | None | None | None | N |
| S/L | 0.088 | likely_benign | 0.0826 | benign | -0.325 | Destabilizing | 0.003 | N | 0.689 | prob.neutral | None | None | None | None | N |
| S/M | 0.1627 | likely_benign | 0.1488 | benign | -0.638 | Destabilizing | 0.214 | N | 0.697 | prob.neutral | None | None | None | None | N |
| S/N | 0.2397 | likely_benign | 0.2031 | benign | -1.318 | Destabilizing | 0.055 | N | 0.624 | neutral | N | 0.477938923 | None | None | N |
| S/P | 0.9376 | likely_pathogenic | 0.9301 | pathogenic | -0.605 | Destabilizing | 0.136 | N | 0.711 | prob.delet. | None | None | None | None | N |
| S/Q | 0.4843 | ambiguous | 0.4356 | ambiguous | -1.025 | Destabilizing | 0.356 | N | 0.679 | prob.neutral | None | None | None | None | N |
| S/R | 0.3401 | ambiguous | 0.2962 | benign | -1.01 | Destabilizing | 0.055 | N | 0.721 | prob.delet. | N | 0.438055148 | None | None | N |
| S/T | 0.0715 | likely_benign | 0.0669 | benign | -0.975 | Destabilizing | None | N | 0.196 | neutral | N | 0.46272152 | None | None | N |
| S/V | 0.1479 | likely_benign | 0.1376 | benign | -0.605 | Destabilizing | None | N | 0.491 | neutral | None | None | None | None | N |
| S/W | 0.2659 | likely_benign | 0.2479 | benign | -1.136 | Destabilizing | 0.864 | D | 0.733 | prob.delet. | None | None | None | None | N |
| S/Y | 0.1621 | likely_benign | 0.1505 | benign | -0.736 | Destabilizing | 0.356 | N | 0.727 | 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.