Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 1710 | 5353;5354;5355 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| N2AB | 1710 | 5353;5354;5355 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| N2A | 1710 | 5353;5354;5355 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| N2B | 1664 | 5215;5216;5217 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| Novex-1 | 1664 | 5215;5216;5217 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| Novex-2 | 1664 | 5215;5216;5217 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
| Novex-3 | 1710 | 5353;5354;5355 | chr2:178776736;178776735;178776734 | chr2:179641463;179641462;179641461 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | None | None | 0.51 | N | 0.456 | 0.096 | 0.137902524267 | gnomAD-4.0.0 | 1.36819E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-06 | 0 | 0 |
| T/P | rs1331457473  |
-0.618 | 0.973 | N | 0.771 | 0.334 | 0.346544149963 | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.85E-06 | 0 |
| T/P | rs1331457473 |
-0.618 | 0.973 | N | 0.771 | 0.334 | 0.346544149963 | gnomAD-4.0.0 | 6.84097E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99294E-07 | 0 | 0 |
| T/S | None | None | 0.016 | N | 0.292 | 0.111 | 0.130388298395 | gnomAD-4.0.0 | 1.36819E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79859E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.105 | likely_benign | 0.1031 | benign | -0.477 | Destabilizing | 0.51 | D | 0.456 | neutral | N | 0.482348844 | None | None | I |
| T/C | 0.5835 | likely_pathogenic | 0.5486 | ambiguous | -0.426 | Destabilizing | 0.994 | D | 0.707 | prob.neutral | None | None | None | None | I |
| T/D | 0.6199 | likely_pathogenic | 0.563 | ambiguous | 0.597 | Stabilizing | 0.959 | D | 0.675 | neutral | None | None | None | None | I |
| T/E | 0.5704 | likely_pathogenic | 0.5166 | ambiguous | 0.553 | Stabilizing | 0.921 | D | 0.666 | neutral | None | None | None | None | I |
| T/F | 0.5015 | ambiguous | 0.4448 | ambiguous | -0.938 | Destabilizing | 0.979 | D | 0.755 | deleterious | None | None | None | None | I |
| T/G | 0.2391 | likely_benign | 0.2453 | benign | -0.624 | Destabilizing | 0.769 | D | 0.578 | neutral | None | None | None | None | I |
| T/H | 0.426 | ambiguous | 0.3657 | ambiguous | -0.818 | Destabilizing | 0.994 | D | 0.709 | prob.delet. | None | None | None | None | I |
| T/I | 0.3362 | likely_benign | 0.3027 | benign | -0.204 | Destabilizing | 0.946 | D | 0.77 | deleterious | N | 0.504786338 | None | None | I |
| T/K | 0.5244 | ambiguous | 0.4704 | ambiguous | -0.211 | Destabilizing | 0.921 | D | 0.675 | prob.neutral | None | None | None | None | I |
| T/L | 0.1848 | likely_benign | 0.1745 | benign | -0.204 | Destabilizing | 0.87 | D | 0.61 | neutral | None | None | None | None | I |
| T/M | 0.1744 | likely_benign | 0.1655 | benign | -0.222 | Destabilizing | 0.998 | D | 0.727 | prob.delet. | None | None | None | None | I |
| T/N | 0.1482 | likely_benign | 0.1457 | benign | -0.144 | Destabilizing | 0.898 | D | 0.621 | neutral | N | 0.445140607 | None | None | I |
| T/P | 0.267 | likely_benign | 0.3004 | benign | -0.266 | Destabilizing | 0.973 | D | 0.771 | deleterious | N | 0.491258547 | None | None | I |
| T/Q | 0.3642 | ambiguous | 0.3377 | benign | -0.263 | Destabilizing | 0.959 | D | 0.761 | deleterious | None | None | None | None | I |
| T/R | 0.5208 | ambiguous | 0.4332 | ambiguous | -0.033 | Destabilizing | 0.959 | D | 0.767 | deleterious | None | None | None | None | I |
| T/S | 0.0967 | likely_benign | 0.0949 | benign | -0.425 | Destabilizing | 0.016 | N | 0.292 | neutral | N | 0.393450058 | None | None | I |
| T/V | 0.2197 | likely_benign | 0.2102 | benign | -0.266 | Destabilizing | 0.87 | D | 0.541 | neutral | None | None | None | None | I |
| T/W | 0.8623 | likely_pathogenic | 0.8144 | pathogenic | -0.935 | Destabilizing | 0.998 | D | 0.705 | prob.neutral | None | None | None | None | I |
| T/Y | 0.5589 | ambiguous | 0.4932 | ambiguous | -0.632 | Destabilizing | 0.993 | D | 0.743 | deleterious | None | None | 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.