Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22225 | 66898;66899;66900 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| N2AB | 20584 | 61975;61976;61977 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| N2A | 19657 | 59194;59195;59196 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| N2B | 13160 | 39703;39704;39705 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| Novex-1 | 13285 | 40078;40079;40080 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| Novex-2 | 13352 | 40279;40280;40281 | chr2:178581595;178581594;178581593 | chr2:179446322;179446321;179446320 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/N | rs72646870  |
-0.215 | None | N | 0.158 | 0.065 | None | gnomAD-2.1.1 | 1.89742E-04 | None | None | None | None | N | None | 1.65426E-04 | 2.83E-05 | None | 0 | 0 | None | 0 | None | 0 | 3.76158E-04 | 0 |
| D/N | rs72646870 |
-0.215 | None | N | 0.158 | 0.065 | None | gnomAD-3.1.2 | 3.09093E-04 | None | None | None | None | N | None | 9.65E-05 | 1.96618E-04 | 0 | 0 | 0 | None | 0 | 0 | 5.8846E-04 | 0 | 0 |
| D/N | rs72646870 |
-0.215 | None | N | 0.158 | 0.065 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| D/N | rs72646870 |
-0.215 | None | N | 0.158 | 0.065 | None | gnomAD-4.0.0 | 3.60894E-04 | None | None | None | None | N | None | 1.06698E-04 | 6.67178E-05 | None | 0 | 0 | None | 0 | 0 | 4.59662E-04 | 0 | 4.48646E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.2368 | likely_benign | 0.2103 | benign | -0.278 | Destabilizing | 0.052 | N | 0.539 | neutral | N | 0.43492163 | None | None | N |
| D/C | 0.636 | likely_pathogenic | 0.6219 | pathogenic | -0.224 | Destabilizing | 0.935 | D | 0.537 | neutral | None | None | None | None | N |
| D/E | 0.1934 | likely_benign | 0.1626 | benign | -0.291 | Destabilizing | 0.027 | N | 0.391 | neutral | N | 0.45835585 | None | None | N |
| D/F | 0.6649 | likely_pathogenic | 0.67 | pathogenic | -0.095 | Destabilizing | 0.791 | D | 0.544 | neutral | None | None | None | None | N |
| D/G | 0.1097 | likely_benign | 0.1045 | benign | -0.474 | Destabilizing | None | N | 0.215 | neutral | N | 0.358492713 | None | None | N |
| D/H | 0.2631 | likely_benign | 0.2557 | benign | 0.27 | Stabilizing | 0.317 | N | 0.457 | neutral | N | 0.468148769 | None | None | N |
| D/I | 0.5821 | likely_pathogenic | 0.5485 | ambiguous | 0.194 | Stabilizing | 0.555 | D | 0.549 | neutral | None | None | None | None | N |
| D/K | 0.3248 | likely_benign | 0.3108 | benign | 0.179 | Stabilizing | 0.081 | N | 0.456 | neutral | None | None | None | None | N |
| D/L | 0.4836 | ambiguous | 0.4721 | ambiguous | 0.194 | Stabilizing | 0.149 | N | 0.546 | neutral | None | None | None | None | N |
| D/M | 0.6466 | likely_pathogenic | 0.6151 | pathogenic | 0.13 | Stabilizing | 0.935 | D | 0.525 | neutral | None | None | None | None | N |
| D/N | 0.0681 | likely_benign | 0.0685 | benign | -0.159 | Destabilizing | None | N | 0.158 | neutral | N | 0.371102225 | None | None | N |
| D/P | 0.8236 | likely_pathogenic | 0.8135 | pathogenic | 0.058 | Stabilizing | 0.555 | D | 0.469 | neutral | None | None | None | None | N |
| D/Q | 0.3418 | ambiguous | 0.3215 | benign | -0.113 | Destabilizing | 0.38 | N | 0.383 | neutral | None | None | None | None | N |
| D/R | 0.4201 | ambiguous | 0.4122 | ambiguous | 0.49 | Stabilizing | 0.149 | N | 0.534 | neutral | None | None | None | None | N |
| D/S | 0.1478 | likely_benign | 0.1392 | benign | -0.281 | Destabilizing | 0.035 | N | 0.4 | neutral | None | None | None | None | N |
| D/T | 0.3148 | likely_benign | 0.2813 | benign | -0.122 | Destabilizing | 0.081 | N | 0.448 | neutral | None | None | None | None | N |
| D/V | 0.4237 | ambiguous | 0.3845 | ambiguous | 0.058 | Stabilizing | 0.484 | N | 0.537 | neutral | N | 0.517577512 | None | None | N |
| D/W | 0.9004 | likely_pathogenic | 0.8988 | pathogenic | 0.062 | Stabilizing | 0.935 | D | 0.628 | neutral | None | None | None | None | N |
| D/Y | 0.2422 | likely_benign | 0.2563 | benign | 0.148 | Stabilizing | 0.741 | D | 0.542 | neutral | N | 0.447485495 | 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.