Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 2836 | 8731;8732;8733 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| N2AB | 2836 | 8731;8732;8733 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| N2A | 2836 | 8731;8732;8733 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| N2B | 2790 | 8593;8594;8595 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| Novex-1 | 2790 | 8593;8594;8595 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| Novex-2 | 2790 | 8593;8594;8595 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
| Novex-3 | 2836 | 8731;8732;8733 | chr2:178770195;178770194;178770193 | chr2:179634922;179634921;179634920 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1310170063  |
-0.145 | 0.896 | N | 0.506 | 0.343 | 0.683537019701 | gnomAD-2.1.1 | 3.98E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| P/L | rs1310170063 |
-0.145 | 0.896 | N | 0.506 | 0.343 | 0.683537019701 | gnomAD-4.0.0 | 1.59046E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43271E-05 | 0 |
| P/R | rs1310170063 |
None | 0.938 | D | 0.571 | 0.364 | 0.58191536258 | gnomAD-4.0.0 | 3.18092E-06 | None | None | None | None | N | None | 0 | 0 | None | 4.76554E-05 | 0 | None | 0 | 0 | 2.85649E-06 | 0 | 0 |
| P/T | rs772547332 |
-0.486 | 0.811 | N | 0.453 | 0.267 | 0.464528537357 | gnomAD-2.1.1 | 7.08E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 7.96E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0881 | likely_benign | 0.0916 | benign | -0.552 | Destabilizing | 0.103 | N | 0.288 | neutral | N | 0.50411833 | None | None | N |
| P/C | 0.6659 | likely_pathogenic | 0.7461 | pathogenic | -0.721 | Destabilizing | 0.999 | D | 0.642 | neutral | None | None | None | None | N |
| P/D | 0.5347 | ambiguous | 0.5828 | pathogenic | -0.376 | Destabilizing | 0.919 | D | 0.428 | neutral | None | None | None | None | N |
| P/E | 0.3489 | ambiguous | 0.396 | ambiguous | -0.467 | Destabilizing | 0.851 | D | 0.441 | neutral | None | None | None | None | N |
| P/F | 0.6832 | likely_pathogenic | 0.739 | pathogenic | -0.674 | Destabilizing | 0.996 | D | 0.619 | neutral | None | None | None | None | N |
| P/G | 0.3852 | ambiguous | 0.4343 | ambiguous | -0.703 | Destabilizing | 0.919 | D | 0.459 | neutral | None | None | None | None | N |
| P/H | 0.3053 | likely_benign | 0.3422 | ambiguous | -0.202 | Destabilizing | 0.997 | D | 0.589 | neutral | None | None | None | None | N |
| P/I | 0.4542 | ambiguous | 0.5128 | ambiguous | -0.29 | Destabilizing | 0.988 | D | 0.614 | neutral | None | None | None | None | N |
| P/K | 0.4467 | ambiguous | 0.5105 | ambiguous | -0.564 | Destabilizing | 0.851 | D | 0.447 | neutral | None | None | None | None | N |
| P/L | 0.183 | likely_benign | 0.2023 | benign | -0.29 | Destabilizing | 0.896 | D | 0.506 | neutral | N | 0.508103218 | None | None | N |
| P/M | 0.4107 | ambiguous | 0.4796 | ambiguous | -0.457 | Destabilizing | 0.997 | D | 0.585 | neutral | None | None | None | None | N |
| P/N | 0.3897 | ambiguous | 0.4474 | ambiguous | -0.347 | Destabilizing | 0.976 | D | 0.556 | neutral | None | None | None | None | N |
| P/Q | 0.1993 | likely_benign | 0.2373 | benign | -0.551 | Destabilizing | 0.211 | N | 0.304 | neutral | N | 0.502620696 | None | None | N |
| P/R | 0.3198 | likely_benign | 0.3498 | ambiguous | -0.053 | Destabilizing | 0.938 | D | 0.571 | neutral | D | 0.527586317 | None | None | N |
| P/S | 0.1589 | likely_benign | 0.1749 | benign | -0.714 | Destabilizing | 0.251 | N | 0.256 | neutral | N | 0.502567029 | None | None | N |
| P/T | 0.1449 | likely_benign | 0.1618 | benign | -0.7 | Destabilizing | 0.811 | D | 0.453 | neutral | N | 0.506882758 | None | None | N |
| P/V | 0.294 | likely_benign | 0.3384 | benign | -0.343 | Destabilizing | 0.976 | D | 0.466 | neutral | None | None | None | None | N |
| P/W | 0.8146 | likely_pathogenic | 0.8438 | pathogenic | -0.764 | Destabilizing | 0.999 | D | 0.665 | neutral | None | None | None | None | N |
| P/Y | 0.5852 | likely_pathogenic | 0.6394 | pathogenic | -0.476 | Destabilizing | 0.996 | D | 0.624 | neutral | 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.