Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31751 | 95476;95477;95478 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| N2AB | 30110 | 90553;90554;90555 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| N2A | 29183 | 87772;87773;87774 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| N2B | 22686 | 68281;68282;68283 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| Novex-1 | 22811 | 68656;68657;68658 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| Novex-2 | 22878 | 68857;68858;68859 | chr2:178545985;178545984;178545983 | chr2:179410712;179410711;179410710 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs372132740  |
-0.307 | 1.0 | N | 0.67 | 0.574 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/C | rs372132740 |
-0.307 | 1.0 | N | 0.67 | 0.574 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| S/C | rs372132740 |
-0.307 | 1.0 | N | 0.67 | 0.574 | None | gnomAD-4.0.0 | 3.04475E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61474E-06 | 0 | 0 |
| S/G | rs372132740 |
-0.561 | 0.999 | N | 0.418 | 0.29 | 0.247322355667 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.58E-05 | None | 0 | None | 0 | 0 | 0 |
| S/R | rs753420295 |
-0.143 | 1.0 | N | 0.604 | 0.591 | 0.327686398923 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 0 |
| S/R | rs753420295 |
-0.143 | 1.0 | N | 0.604 | 0.591 | 0.327686398923 | gnomAD-4.0.0 | 8.8948E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.07936E-05 | 0 | 1.65678E-05 |
| S/T | rs1223455292 |
-0.209 | 0.999 | N | 0.403 | 0.306 | 0.269558022972 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.89E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.2781 | likely_benign | 0.2556 | benign | -0.192 | Destabilizing | 0.998 | D | 0.413 | neutral | None | None | None | None | N |
| S/C | 0.5644 | likely_pathogenic | 0.5206 | ambiguous | -0.421 | Destabilizing | 1.0 | D | 0.67 | neutral | N | 0.502603772 | None | None | N |
| S/D | 0.9232 | likely_pathogenic | 0.896 | pathogenic | 0.022 | Stabilizing | 0.999 | D | 0.491 | neutral | None | None | None | None | N |
| S/E | 0.956 | likely_pathogenic | 0.9325 | pathogenic | -0.09 | Destabilizing | 0.999 | D | 0.485 | neutral | None | None | None | None | N |
| S/F | 0.8835 | likely_pathogenic | 0.8727 | pathogenic | -0.92 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | N |
| S/G | 0.3106 | likely_benign | 0.2925 | benign | -0.231 | Destabilizing | 0.999 | D | 0.418 | neutral | N | 0.47130093 | None | None | N |
| S/H | 0.8736 | likely_pathogenic | 0.8466 | pathogenic | -0.563 | Destabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | N |
| S/I | 0.8365 | likely_pathogenic | 0.8265 | pathogenic | -0.223 | Destabilizing | 1.0 | D | 0.687 | prob.neutral | N | 0.505971133 | None | None | N |
| S/K | 0.9846 | likely_pathogenic | 0.9747 | pathogenic | -0.402 | Destabilizing | 0.999 | D | 0.485 | neutral | None | None | None | None | N |
| S/L | 0.5126 | ambiguous | 0.4894 | ambiguous | -0.223 | Destabilizing | 1.0 | D | 0.575 | neutral | None | None | None | None | N |
| S/M | 0.7112 | likely_pathogenic | 0.6895 | pathogenic | -0.16 | Destabilizing | 1.0 | D | 0.679 | prob.neutral | None | None | None | None | N |
| S/N | 0.6064 | likely_pathogenic | 0.5913 | pathogenic | -0.188 | Destabilizing | 0.999 | D | 0.473 | neutral | N | 0.515379782 | None | None | N |
| S/P | 0.9383 | likely_pathogenic | 0.9181 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.609 | neutral | None | None | None | None | N |
| S/Q | 0.9127 | likely_pathogenic | 0.8867 | pathogenic | -0.426 | Destabilizing | 1.0 | D | 0.589 | neutral | None | None | None | None | N |
| S/R | 0.9744 | likely_pathogenic | 0.9605 | pathogenic | -0.156 | Destabilizing | 1.0 | D | 0.604 | neutral | N | 0.46625345 | None | None | N |
| S/T | 0.2847 | likely_benign | 0.2262 | benign | -0.31 | Destabilizing | 0.999 | D | 0.403 | neutral | N | 0.474736146 | None | None | N |
| S/V | 0.7557 | likely_pathogenic | 0.7304 | pathogenic | -0.19 | Destabilizing | 1.0 | D | 0.669 | neutral | None | None | None | None | N |
| S/W | 0.9107 | likely_pathogenic | 0.8991 | pathogenic | -0.987 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| S/Y | 0.8476 | likely_pathogenic | 0.8363 | pathogenic | -0.678 | Destabilizing | 1.0 | D | 0.728 | 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.