Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 26611 | 80056;80057;80058 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| N2AB | 24970 | 75133;75134;75135 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| N2A | 24043 | 72352;72353;72354 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| N2B | 17546 | 52861;52862;52863 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| Novex-1 | 17671 | 53236;53237;53238 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| Novex-2 | 17738 | 53437;53438;53439 | chr2:178566301;178566300;178566299 | chr2:179431028;179431027;179431026 |
| 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 | rs745409995  |
-0.487 | 1.0 | N | 0.671 | 0.493 | 0.452450644169 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.77E-05 | 0 |
| R/G | rs745409995 |
-0.487 | 1.0 | N | 0.671 | 0.493 | 0.452450644169 | gnomAD-4.0.0 | 3.76337E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.94737E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6676 | likely_pathogenic | 0.5508 | ambiguous | -0.446 | Destabilizing | 0.999 | D | 0.623 | neutral | None | None | None | None | N |
| R/C | 0.2625 | likely_benign | 0.2129 | benign | -0.431 | Destabilizing | 1.0 | D | 0.754 | deleterious | None | None | None | None | N |
| R/D | 0.8916 | likely_pathogenic | 0.8368 | pathogenic | -0.061 | Destabilizing | 1.0 | D | 0.72 | prob.delet. | None | None | None | None | N |
| R/E | 0.6618 | likely_pathogenic | 0.5602 | ambiguous | -0.003 | Destabilizing | 0.999 | D | 0.646 | neutral | None | None | None | None | N |
| R/F | 0.6938 | likely_pathogenic | 0.5819 | pathogenic | -0.675 | Destabilizing | 1.0 | D | 0.731 | prob.delet. | None | None | None | None | N |
| R/G | 0.6099 | likely_pathogenic | 0.5075 | ambiguous | -0.652 | Destabilizing | 1.0 | D | 0.671 | neutral | N | 0.487799247 | None | None | N |
| R/H | 0.1385 | likely_benign | 0.1191 | benign | -0.993 | Destabilizing | 1.0 | D | 0.761 | deleterious | None | None | None | None | N |
| R/I | 0.3793 | ambiguous | 0.2886 | benign | 0.068 | Stabilizing | 1.0 | D | 0.728 | prob.delet. | N | 0.459273285 | None | None | N |
| R/K | 0.1221 | likely_benign | 0.1163 | benign | -0.406 | Destabilizing | 0.997 | D | 0.543 | neutral | N | 0.451778094 | None | None | N |
| R/L | 0.4243 | ambiguous | 0.3408 | ambiguous | 0.068 | Stabilizing | 1.0 | D | 0.671 | neutral | None | None | None | None | N |
| R/M | 0.4246 | ambiguous | 0.3368 | benign | -0.115 | Destabilizing | 1.0 | D | 0.75 | deleterious | None | None | None | None | N |
| R/N | 0.7767 | likely_pathogenic | 0.6865 | pathogenic | 0.07 | Stabilizing | 1.0 | D | 0.744 | deleterious | None | None | None | None | N |
| R/P | 0.9673 | likely_pathogenic | 0.9544 | pathogenic | -0.084 | Destabilizing | 1.0 | D | 0.714 | prob.delet. | None | None | None | None | N |
| R/Q | 0.161 | likely_benign | 0.1386 | benign | -0.194 | Destabilizing | 1.0 | D | 0.743 | deleterious | None | None | None | None | N |
| R/S | 0.7177 | likely_pathogenic | 0.6038 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.708 | prob.delet. | N | 0.452538562 | None | None | N |
| R/T | 0.4013 | ambiguous | 0.3052 | benign | -0.345 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | N | 0.48469901 | None | None | N |
| R/V | 0.4355 | ambiguous | 0.3444 | ambiguous | -0.084 | Destabilizing | 1.0 | D | 0.722 | prob.delet. | None | None | None | None | N |
| R/W | 0.293 | likely_benign | 0.2428 | benign | -0.542 | Destabilizing | 1.0 | D | 0.757 | deleterious | None | None | None | None | N |
| R/Y | 0.5567 | ambiguous | 0.4648 | ambiguous | -0.169 | Destabilizing | 1.0 | D | 0.737 | prob.delet. | 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.