Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14079 | 42460;42461;42462 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| N2AB | 12438 | 37537;37538;37539 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| N2A | 11511 | 34756;34757;34758 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| N2B | 5014 | 15265;15266;15267 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| Novex-1 | 5139 | 15640;15641;15642 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| Novex-2 | 5206 | 15841;15842;15843 | chr2:178634546;178634545;178634544 | chr2:179499273;179499272;179499271 |
| 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/G | rs745926057  |
-0.347 | 0.983 | N | 0.465 | 0.283 | 0.312001716656 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| R/G | rs745926057 |
-0.347 | 0.983 | N | 0.465 | 0.283 | 0.312001716656 | gnomAD-4.0.0 | 2.05317E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47883E-05 | 0 |
| R/L | rs746480872 |
None | 0.983 | N | 0.465 | 0.405 | 0.664074601257 | gnomAD-4.0.0 | 1.36878E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.31927E-05 | 0 |
| R/Q | None | 0.299 | 0.716 | N | 0.281 | 0.302 | 0.193865811164 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 5.8E-05 | None | 0 | 0 | None | 0 | None | 0 | 5.35E-05 | 0 |
| R/Q | None | 0.299 | 0.716 | N | 0.281 | 0.302 | 0.193865811164 | gnomAD-4.0.0 | 6.84389E-05 | None | None | None | None | N | None | 0 | 1.56593E-04 | None | 0 | 1.00903E-04 | None | 0 | 0 | 7.55703E-05 | 1.15964E-05 | 6.62932E-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 | 0.8704 | likely_pathogenic | 0.9216 | pathogenic | 0.065 | Stabilizing | 0.863 | D | 0.387 | neutral | None | None | None | None | N |
| R/C | 0.7269 | likely_pathogenic | 0.8036 | pathogenic | -0.105 | Destabilizing | 0.999 | D | 0.455 | neutral | None | None | None | None | N |
| R/D | 0.9638 | likely_pathogenic | 0.9764 | pathogenic | -0.102 | Destabilizing | 0.939 | D | 0.483 | neutral | None | None | None | None | N |
| R/E | 0.7675 | likely_pathogenic | 0.841 | pathogenic | -0.019 | Destabilizing | 0.759 | D | 0.389 | neutral | None | None | None | None | N |
| R/F | 0.9744 | likely_pathogenic | 0.9784 | pathogenic | -0.057 | Destabilizing | 0.997 | D | 0.471 | neutral | None | None | None | None | N |
| R/G | 0.7514 | likely_pathogenic | 0.83 | pathogenic | -0.156 | Destabilizing | 0.983 | D | 0.465 | neutral | N | 0.429223845 | None | None | N |
| R/H | 0.4693 | ambiguous | 0.527 | ambiguous | -0.701 | Destabilizing | 0.991 | D | 0.403 | neutral | None | None | None | None | N |
| R/I | 0.8889 | likely_pathogenic | 0.9184 | pathogenic | 0.619 | Stabilizing | 0.997 | D | 0.481 | neutral | None | None | None | None | N |
| R/K | 0.2609 | likely_benign | 0.2732 | benign | -0.02 | Destabilizing | 0.079 | N | 0.123 | neutral | None | None | None | None | N |
| R/L | 0.8124 | likely_pathogenic | 0.8551 | pathogenic | 0.619 | Stabilizing | 0.983 | D | 0.465 | neutral | N | 0.502359892 | None | None | N |
| R/M | 0.8668 | likely_pathogenic | 0.9045 | pathogenic | 0.063 | Stabilizing | 0.997 | D | 0.445 | neutral | None | None | None | None | N |
| R/N | 0.9537 | likely_pathogenic | 0.9655 | pathogenic | 0.151 | Stabilizing | 0.969 | D | 0.417 | neutral | None | None | None | None | N |
| R/P | 0.9731 | likely_pathogenic | 0.9855 | pathogenic | 0.456 | Stabilizing | 0.998 | D | 0.473 | neutral | N | 0.504974046 | None | None | N |
| R/Q | 0.3095 | likely_benign | 0.3916 | ambiguous | 0.107 | Stabilizing | 0.716 | D | 0.281 | neutral | N | 0.494810126 | None | None | N |
| R/S | 0.9174 | likely_pathogenic | 0.9496 | pathogenic | -0.152 | Destabilizing | 0.939 | D | 0.4 | neutral | None | None | None | None | N |
| R/T | 0.8236 | likely_pathogenic | 0.8794 | pathogenic | 0.076 | Stabilizing | 0.969 | D | 0.442 | neutral | None | None | None | None | N |
| R/V | 0.8856 | likely_pathogenic | 0.922 | pathogenic | 0.456 | Stabilizing | 0.969 | D | 0.501 | neutral | None | None | None | None | N |
| R/W | 0.7666 | likely_pathogenic | 0.799 | pathogenic | -0.115 | Destabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | N |
| R/Y | 0.9293 | likely_pathogenic | 0.9427 | pathogenic | 0.288 | Stabilizing | 0.997 | D | 0.462 | 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.