Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23113 | 69562;69563;69564 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| N2AB | 21472 | 64639;64640;64641 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| N2A | 20545 | 61858;61859;61860 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| N2B | 14048 | 42367;42368;42369 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| Novex-1 | 14173 | 42742;42743;42744 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| Novex-2 | 14240 | 42943;42944;42945 | chr2:178576998;178576997;178576996 | chr2:179441725;179441724;179441723 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs370890454  |
-1.019 | 1.0 | N | 0.805 | 0.466 | None | gnomAD-2.1.1 | 8.59E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.80588E-04 | 1.40805E-04 |
| R/Q | rs370890454 |
-1.019 | 1.0 | N | 0.805 | 0.466 | None | gnomAD-3.1.2 | 1.18395E-04 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.35329E-04 | 0 | 0 |
| R/Q | rs370890454 |
-1.019 | 1.0 | N | 0.805 | 0.466 | None | gnomAD-4.0.0 | 2.26862E-04 | None | None | None | None | N | None | 6.67789E-05 | 1.66772E-05 | None | 0 | 0 | None | 0 | 0 | 2.78067E-04 | 1.09815E-05 | 4.96429E-04 |
| R/W | rs749409444 |
-0.694 | 1.0 | D | 0.774 | 0.642 | 0.720684183395 | gnomAD-2.1.1 | 6.05E-05 | None | None | None | None | N | None | 0 | 3.76659E-04 | None | 0 | 0 | None | 0 | None | 0 | 0 | 3.32116E-04 |
| R/W | rs749409444 |
-0.694 | 1.0 | D | 0.774 | 0.642 | 0.720684183395 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/W | rs749409444 |
-0.694 | 1.0 | D | 0.774 | 0.642 | 0.720684183395 | gnomAD-4.0.0 | 1.30172E-05 | None | None | None | None | N | None | 1.33611E-05 | 2.3345E-04 | None | 0 | 2.23045E-05 | None | 0 | 0 | 3.39111E-06 | 0 | 1.60154E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.9539 | likely_pathogenic | 0.9636 | pathogenic | -1.74 | Destabilizing | 0.999 | D | 0.632 | neutral | None | None | None | None | N |
| R/C | 0.481 | ambiguous | 0.5485 | ambiguous | -1.715 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/D | 0.9967 | likely_pathogenic | 0.9966 | pathogenic | -0.977 | Destabilizing | 1.0 | D | 0.8 | deleterious | None | None | None | None | N |
| R/E | 0.9509 | likely_pathogenic | 0.9571 | pathogenic | -0.759 | Destabilizing | 0.999 | D | 0.691 | prob.neutral | None | None | None | None | N |
| R/F | 0.985 | likely_pathogenic | 0.9845 | pathogenic | -0.867 | Destabilizing | 1.0 | D | 0.839 | deleterious | None | None | None | None | N |
| R/G | 0.9414 | likely_pathogenic | 0.9516 | pathogenic | -2.088 | Highly Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.555629998 | None | None | N |
| R/H | 0.4148 | ambiguous | 0.4106 | ambiguous | -1.943 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| R/I | 0.9345 | likely_pathogenic | 0.9437 | pathogenic | -0.735 | Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| R/K | 0.4459 | ambiguous | 0.461 | ambiguous | -1.23 | Destabilizing | 0.998 | D | 0.657 | neutral | None | None | None | None | N |
| R/L | 0.8872 | likely_pathogenic | 0.9014 | pathogenic | -0.735 | Destabilizing | 1.0 | D | 0.743 | deleterious | D | 0.527904184 | None | None | N |
| R/M | 0.9215 | likely_pathogenic | 0.9389 | pathogenic | -1.291 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/N | 0.9851 | likely_pathogenic | 0.9846 | pathogenic | -1.3 | Destabilizing | 1.0 | D | 0.799 | deleterious | None | None | None | None | N |
| R/P | 0.9993 | likely_pathogenic | 0.9995 | pathogenic | -1.059 | Destabilizing | 1.0 | D | 0.807 | deleterious | D | 0.567657866 | None | None | N |
| R/Q | 0.3123 | likely_benign | 0.356 | ambiguous | -1.086 | Destabilizing | 1.0 | D | 0.805 | deleterious | N | 0.517558156 | None | None | N |
| R/S | 0.9647 | likely_pathogenic | 0.9649 | pathogenic | -2.08 | Highly Destabilizing | 1.0 | D | 0.749 | deleterious | None | None | None | None | N |
| R/T | 0.9459 | likely_pathogenic | 0.9535 | pathogenic | -1.654 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/V | 0.9448 | likely_pathogenic | 0.9527 | pathogenic | -1.059 | Destabilizing | 1.0 | D | 0.809 | deleterious | None | None | None | None | N |
| R/W | 0.7791 | likely_pathogenic | 0.8 | pathogenic | -0.471 | Destabilizing | 1.0 | D | 0.774 | deleterious | D | 0.555883487 | None | None | N |
| R/Y | 0.9462 | likely_pathogenic | 0.9469 | pathogenic | -0.311 | Destabilizing | 1.0 | D | 0.829 | 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.