Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31304 | 94135;94136;94137 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| N2AB | 29663 | 89212;89213;89214 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| N2A | 28736 | 86431;86432;86433 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| N2B | 22239 | 66940;66941;66942 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| Novex-1 | 22364 | 67315;67316;67317 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| Novex-2 | 22431 | 67516;67517;67518 | chr2:178547716;178547715;178547714 | chr2:179412443;179412442;179412441 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/M | rs879165673  |
-0.251 | 0.627 | N | 0.412 | 0.102 | 0.68170140072 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.48E-05 | 0 |
| V/M | rs879165673 |
-0.251 | 0.627 | N | 0.412 | 0.102 | 0.68170140072 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| V/M | rs879165673 |
-0.251 | 0.627 | N | 0.412 | 0.102 | 0.68170140072 | gnomAD-4.0.0 | 2.02989E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40984E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.1965 | likely_benign | 0.17 | benign | -1.125 | Destabilizing | 0.003 | N | 0.095 | neutral | N | 0.416077658 | None | None | N |
| V/C | 0.7452 | likely_pathogenic | 0.6633 | pathogenic | -0.869 | Destabilizing | 0.981 | D | 0.42 | neutral | None | None | None | None | N |
| V/D | 0.4054 | ambiguous | 0.351 | ambiguous | -0.582 | Destabilizing | 0.241 | N | 0.547 | neutral | None | None | None | None | N |
| V/E | 0.2939 | likely_benign | 0.2831 | benign | -0.621 | Destabilizing | 0.324 | N | 0.513 | neutral | N | 0.43737565 | None | None | N |
| V/F | 0.2087 | likely_benign | 0.1968 | benign | -0.93 | Destabilizing | 0.69 | D | 0.471 | neutral | None | None | None | None | N |
| V/G | 0.4069 | ambiguous | 0.3251 | benign | -1.383 | Destabilizing | 0.324 | N | 0.536 | neutral | N | 0.495309233 | None | None | N |
| V/H | 0.497 | ambiguous | 0.4308 | ambiguous | -0.825 | Destabilizing | 0.944 | D | 0.529 | neutral | None | None | None | None | N |
| V/I | 0.0701 | likely_benign | 0.0723 | benign | -0.546 | Destabilizing | 0.001 | N | 0.112 | neutral | None | None | None | None | N |
| V/K | 0.3384 | likely_benign | 0.3305 | benign | -0.821 | Destabilizing | 0.388 | N | 0.513 | neutral | None | None | None | None | N |
| V/L | 0.178 | likely_benign | 0.1651 | benign | -0.546 | Destabilizing | 0.033 | N | 0.342 | neutral | N | 0.44243754 | None | None | N |
| V/M | 0.1178 | likely_benign | 0.1185 | benign | -0.458 | Destabilizing | 0.627 | D | 0.412 | neutral | N | 0.47680083 | None | None | N |
| V/N | 0.2113 | likely_benign | 0.1834 | benign | -0.601 | Destabilizing | 0.008 | N | 0.425 | neutral | None | None | None | None | N |
| V/P | 0.9602 | likely_pathogenic | 0.9387 | pathogenic | -0.702 | Destabilizing | 0.818 | D | 0.525 | neutral | None | None | None | None | N |
| V/Q | 0.3087 | likely_benign | 0.277 | benign | -0.807 | Destabilizing | 0.818 | D | 0.545 | neutral | None | None | None | None | N |
| V/R | 0.3087 | likely_benign | 0.282 | benign | -0.31 | Destabilizing | 0.818 | D | 0.565 | neutral | None | None | None | None | N |
| V/S | 0.2177 | likely_benign | 0.1764 | benign | -1.154 | Destabilizing | 0.116 | N | 0.494 | neutral | None | None | None | None | N |
| V/T | 0.1307 | likely_benign | 0.1262 | benign | -1.085 | Destabilizing | 0.008 | N | 0.165 | neutral | None | None | None | None | N |
| V/W | 0.8315 | likely_pathogenic | 0.7924 | pathogenic | -1.029 | Destabilizing | 0.981 | D | 0.621 | neutral | None | None | None | None | N |
| V/Y | 0.5316 | ambiguous | 0.471 | ambiguous | -0.738 | Destabilizing | 0.818 | D | 0.469 | 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.