Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 32322 | 97189;97190;97191 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| N2AB | 30681 | 92266;92267;92268 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| N2A | 29754 | 89485;89486;89487 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| N2B | 23257 | 69994;69995;69996 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| Novex-1 | 23382 | 70369;70370;70371 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| Novex-2 | 23449 | 70570;70571;70572 | chr2:178542890;178542889;178542888 | chr2:179407617;179407616;179407615 |
| 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/T | rs1187427678  |
-0.107 | 0.549 | N | 0.475 | 0.126 | 0.18995819373 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| R/T | rs1187427678 |
-0.107 | 0.549 | N | 0.475 | 0.126 | 0.18995819373 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/T | rs1187427678 |
-0.107 | 0.549 | N | 0.475 | 0.126 | 0.18995819373 | gnomAD-4.0.0 | 4.33847E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.93431E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.5096 | ambiguous | 0.4085 | ambiguous | 0.06 | Stabilizing | 0.25 | N | 0.439 | neutral | None | None | None | None | I |
| R/C | 0.2429 | likely_benign | 0.2138 | benign | -0.129 | Destabilizing | 0.992 | D | 0.481 | neutral | None | None | None | None | I |
| R/D | 0.748 | likely_pathogenic | 0.6768 | pathogenic | -0.143 | Destabilizing | 0.617 | D | 0.442 | neutral | None | None | None | None | I |
| R/E | 0.4409 | ambiguous | 0.3737 | ambiguous | -0.072 | Destabilizing | 0.25 | N | 0.464 | neutral | None | None | None | None | I |
| R/F | 0.6045 | likely_pathogenic | 0.5274 | ambiguous | -0.152 | Destabilizing | 0.972 | D | 0.452 | neutral | None | None | None | None | I |
| R/G | 0.3741 | ambiguous | 0.2682 | benign | -0.141 | Destabilizing | 0.549 | D | 0.465 | neutral | N | 0.375648748 | None | None | I |
| R/H | 0.1181 | likely_benign | 0.1028 | benign | -0.718 | Destabilizing | 0.92 | D | 0.43 | neutral | None | None | None | None | I |
| R/I | 0.3486 | ambiguous | 0.2956 | benign | 0.554 | Stabilizing | 0.896 | D | 0.456 | neutral | N | 0.446954272 | None | None | I |
| R/K | 0.0936 | likely_benign | 0.0764 | benign | -0.062 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.336130354 | None | None | I |
| R/L | 0.2891 | likely_benign | 0.2309 | benign | 0.554 | Stabilizing | 0.617 | D | 0.465 | neutral | None | None | None | None | I |
| R/M | 0.326 | likely_benign | 0.2483 | benign | 0.057 | Stabilizing | 0.972 | D | 0.426 | neutral | None | None | None | None | I |
| R/N | 0.5713 | likely_pathogenic | 0.4882 | ambiguous | 0.107 | Stabilizing | 0.617 | D | 0.479 | neutral | None | None | None | None | I |
| R/P | 0.9175 | likely_pathogenic | 0.8619 | pathogenic | 0.41 | Stabilizing | 0.92 | D | 0.45 | neutral | None | None | None | None | I |
| R/Q | 0.1063 | likely_benign | 0.0948 | benign | 0.053 | Stabilizing | 0.447 | N | 0.515 | neutral | None | None | None | None | I |
| R/S | 0.5229 | ambiguous | 0.4203 | ambiguous | -0.175 | Destabilizing | 0.379 | N | 0.465 | neutral | N | 0.350713018 | None | None | I |
| R/T | 0.3268 | likely_benign | 0.2454 | benign | 0.033 | Stabilizing | 0.549 | D | 0.475 | neutral | N | 0.374630027 | None | None | I |
| R/V | 0.4192 | ambiguous | 0.3518 | ambiguous | 0.41 | Stabilizing | 0.85 | D | 0.423 | neutral | None | None | None | None | I |
| R/W | 0.3054 | likely_benign | 0.2296 | benign | -0.244 | Destabilizing | 0.992 | D | 0.566 | neutral | None | None | None | None | I |
| R/Y | 0.4617 | ambiguous | 0.4073 | ambiguous | 0.173 | Stabilizing | 0.972 | D | 0.454 | neutral | 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.