Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16392 | 49399;49400;49401 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| N2AB | 14751 | 44476;44477;44478 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| N2A | 13824 | 41695;41696;41697 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| N2B | 7327 | 22204;22205;22206 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| Novex-1 | 7452 | 22579;22580;22581 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| Novex-2 | 7519 | 22780;22781;22782 | chr2:178614223;178614222;178614221 | chr2:179478950;179478949;179478948 |
| 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/E | rs750310775  |
-2.29 | 1.0 | N | 0.787 | 0.306 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| A/E | rs750310775 |
-2.29 | 1.0 | N | 0.787 | 0.306 | None | gnomAD-4.0.0 | 1.30084E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.61963E-05 | 0 | 1.65843E-05 |
| A/T | rs794729446 |
None | 1.0 | N | 0.699 | 0.288 | 0.325533332567 | gnomAD-4.0.0 | 1.59368E-06 | None | None | None | None | N | None | 5.67151E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.5359 | ambiguous | 0.5271 | ambiguous | -1.398 | Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| A/D | 0.3398 | likely_benign | 0.271 | benign | -2.182 | Highly Destabilizing | 1.0 | D | 0.776 | deleterious | None | None | None | None | N |
| A/E | 0.3218 | likely_benign | 0.2635 | benign | -2.14 | Highly Destabilizing | 1.0 | D | 0.787 | deleterious | N | 0.347813179 | None | None | N |
| A/F | 0.4857 | ambiguous | 0.4351 | ambiguous | -1.174 | Destabilizing | 1.0 | D | 0.78 | deleterious | None | None | None | None | N |
| A/G | 0.1548 | likely_benign | 0.1489 | benign | -1.574 | Destabilizing | 1.0 | D | 0.536 | neutral | N | 0.477792751 | None | None | N |
| A/H | 0.5895 | likely_pathogenic | 0.5482 | ambiguous | -1.691 | Destabilizing | 1.0 | D | 0.753 | deleterious | None | None | None | None | N |
| A/I | 0.3823 | ambiguous | 0.3421 | ambiguous | -0.469 | Destabilizing | 1.0 | D | 0.79 | deleterious | None | None | None | None | N |
| A/K | 0.6567 | likely_pathogenic | 0.5863 | pathogenic | -1.433 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| A/L | 0.2158 | likely_benign | 0.1953 | benign | -0.469 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| A/M | 0.2792 | likely_benign | 0.2517 | benign | -0.512 | Destabilizing | 1.0 | D | 0.742 | deleterious | None | None | None | None | N |
| A/N | 0.2714 | likely_benign | 0.2404 | benign | -1.394 | Destabilizing | 1.0 | D | 0.788 | deleterious | None | None | None | None | N |
| A/P | 0.2163 | likely_benign | 0.1982 | benign | -0.688 | Destabilizing | 1.0 | D | 0.797 | deleterious | N | 0.457676813 | None | None | N |
| A/Q | 0.396 | ambiguous | 0.3612 | ambiguous | -1.503 | Destabilizing | 1.0 | D | 0.794 | deleterious | None | None | None | None | N |
| A/R | 0.6417 | likely_pathogenic | 0.5902 | pathogenic | -1.128 | Destabilizing | 1.0 | D | 0.797 | deleterious | None | None | None | None | N |
| A/S | 0.1015 | likely_benign | 0.0964 | benign | -1.762 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.464968988 | None | None | N |
| A/T | 0.1329 | likely_benign | 0.1228 | benign | -1.625 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | N | 0.459413621 | None | None | N |
| A/V | 0.1994 | likely_benign | 0.1796 | benign | -0.688 | Destabilizing | 1.0 | D | 0.625 | neutral | N | 0.481422485 | None | None | N |
| A/W | 0.8403 | likely_pathogenic | 0.808 | pathogenic | -1.621 | Destabilizing | 1.0 | D | 0.766 | deleterious | None | None | None | None | N |
| A/Y | 0.6259 | likely_pathogenic | 0.5768 | pathogenic | -1.201 | Destabilizing | 1.0 | D | 0.777 | deleterious | 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.