Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31853 | 95782;95783;95784 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| N2AB | 30212 | 90859;90860;90861 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| N2A | 29285 | 88078;88079;88080 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| N2B | 22788 | 68587;68588;68589 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| Novex-1 | 22913 | 68962;68963;68964 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| Novex-2 | 22980 | 69163;69164;69165 | chr2:178545553;178545552;178545551 | chr2:179410280;179410279;179410278 |
| 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/C | rs727503542  |
-0.385 | 0.996 | D | 0.631 | 0.372 | 0.416328079214 | gnomAD-2.1.1 | 1.78E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 3.9E-05 | 0 |
| R/C | rs727503542 |
-0.385 | 0.996 | D | 0.631 | 0.372 | 0.416328079214 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 4.78011E-04 |
| R/C | rs727503542 |
-0.385 | 0.996 | D | 0.631 | 0.372 | 0.416328079214 | gnomAD-4.0.0 | 3.78017E-05 | None | None | None | None | N | None | 6.66524E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.57742E-05 | 0 | 3.20143E-05 |
| R/H | rs754151944 |
-0.896 | 0.02 | N | 0.304 | 0.23 | 0.21737058555 | gnomAD-2.1.1 | 8.2E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 1.02449E-04 | None | 0 | None | 1.19894E-04 | 1.32612E-04 | 0 |
| R/H | rs754151944 |
-0.896 | 0.02 | N | 0.304 | 0.23 | 0.21737058555 | gnomAD-3.1.2 | 1.05161E-04 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.2051E-04 | 0 | 0 |
| R/H | rs754151944 |
-0.896 | 0.02 | N | 0.304 | 0.23 | 0.21737058555 | gnomAD-4.0.0 | 2.29298E-05 | None | None | None | None | N | None | 1.33494E-05 | 1.66689E-05 | None | 0 | 6.68509E-05 | None | 1.24973E-04 | 0 | 1.86486E-05 | 0 | 3.20246E-05 |
| R/S | rs727503542 |
None | 0.561 | N | 0.449 | 0.196 | 0.284150004643 | gnomAD-4.0.0 | 6.84242E-07 | None | None | None | None | N | None | 2.98811E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.8214 | likely_pathogenic | 0.8457 | pathogenic | 0.028 | Stabilizing | 0.399 | N | 0.503 | neutral | None | None | None | None | N |
| R/C | 0.3766 | ambiguous | 0.3685 | ambiguous | -0.208 | Destabilizing | 0.996 | D | 0.631 | neutral | D | 0.523897577 | None | None | N |
| R/D | 0.9434 | likely_pathogenic | 0.9539 | pathogenic | -0.165 | Destabilizing | 0.7 | D | 0.496 | neutral | None | None | None | None | N |
| R/E | 0.8258 | likely_pathogenic | 0.8472 | pathogenic | -0.118 | Destabilizing | 0.25 | N | 0.519 | neutral | None | None | None | None | N |
| R/F | 0.8017 | likely_pathogenic | 0.7975 | pathogenic | -0.269 | Destabilizing | 0.7 | D | 0.588 | neutral | None | None | None | None | N |
| R/G | 0.6968 | likely_pathogenic | 0.7198 | pathogenic | -0.129 | Destabilizing | 0.561 | D | 0.421 | neutral | N | 0.468833889 | None | None | N |
| R/H | 0.2062 | likely_benign | 0.1986 | benign | -0.592 | Destabilizing | 0.02 | N | 0.304 | neutral | N | 0.477547303 | None | None | N |
| R/I | 0.6481 | likely_pathogenic | 0.6069 | pathogenic | 0.396 | Stabilizing | 0.826 | D | 0.591 | neutral | None | None | None | None | N |
| R/K | 0.264 | likely_benign | 0.2595 | benign | -0.098 | Destabilizing | 0.215 | N | 0.535 | neutral | None | None | None | None | N |
| R/L | 0.5748 | likely_pathogenic | 0.5438 | ambiguous | 0.396 | Stabilizing | 0.817 | D | 0.432 | neutral | N | 0.492044349 | None | None | N |
| R/M | 0.7181 | likely_pathogenic | 0.682 | pathogenic | -0.025 | Destabilizing | 0.982 | D | 0.493 | neutral | None | None | None | None | N |
| R/N | 0.8746 | likely_pathogenic | 0.8929 | pathogenic | 0.038 | Stabilizing | 0.25 | N | 0.484 | neutral | None | None | None | None | N |
| R/P | 0.9404 | likely_pathogenic | 0.9479 | pathogenic | 0.292 | Stabilizing | 0.901 | D | 0.513 | neutral | N | 0.493169569 | None | None | N |
| R/Q | 0.2515 | likely_benign | 0.2463 | benign | -0.029 | Destabilizing | 0.7 | D | 0.499 | neutral | None | None | None | None | N |
| R/S | 0.8662 | likely_pathogenic | 0.8847 | pathogenic | -0.223 | Destabilizing | 0.561 | D | 0.449 | neutral | N | 0.467819931 | None | None | N |
| R/T | 0.7417 | likely_pathogenic | 0.7587 | pathogenic | -0.06 | Destabilizing | 0.7 | D | 0.42 | neutral | None | None | None | None | N |
| R/V | 0.7299 | likely_pathogenic | 0.7057 | pathogenic | 0.292 | Stabilizing | 0.826 | D | 0.594 | neutral | None | None | None | None | N |
| R/W | 0.3731 | ambiguous | 0.3234 | benign | -0.407 | Destabilizing | 0.982 | D | 0.652 | neutral | None | None | None | None | N |
| R/Y | 0.5941 | likely_pathogenic | 0.5749 | pathogenic | 0.008 | Stabilizing | 0.539 | D | 0.521 | 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.