Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28957 | 87094;87095;87096 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| N2AB | 27316 | 82171;82172;82173 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| N2A | 26389 | 79390;79391;79392 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| N2B | 19892 | 59899;59900;59901 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| Novex-1 | 20017 | 60274;60275;60276 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| Novex-2 | 20084 | 60475;60476;60477 | chr2:178558590;178558589;178558588 | chr2:179423317;179423316;179423315 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/E | rs777136109  |
-0.395 | 0.198 | N | 0.15 | 0.099 | 0.0551355673512 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| D/E | rs777136109 |
-0.395 | 0.198 | N | 0.15 | 0.099 | 0.0551355673512 | gnomAD-4.0.0 | 3.18352E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.86689E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1631 | likely_benign | 0.165 | benign | -0.698 | Destabilizing | 0.978 | D | 0.512 | neutral | D | 0.523138047 | None | None | N |
| D/C | 0.481 | ambiguous | 0.4939 | ambiguous | 0.004 | Stabilizing | 1.0 | D | 0.686 | prob.neutral | None | None | None | None | N |
| D/E | 0.1185 | likely_benign | 0.1182 | benign | -0.451 | Destabilizing | 0.198 | N | 0.15 | neutral | N | 0.455547618 | None | None | N |
| D/F | 0.4516 | ambiguous | 0.4925 | ambiguous | -0.689 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | None | None | None | None | N |
| D/G | 0.1336 | likely_benign | 0.1334 | benign | -0.925 | Destabilizing | 0.989 | D | 0.514 | neutral | N | 0.512016976 | None | None | N |
| D/H | 0.2159 | likely_benign | 0.2171 | benign | -0.835 | Destabilizing | 1.0 | D | 0.551 | neutral | N | 0.488660114 | None | None | N |
| D/I | 0.3453 | ambiguous | 0.3675 | ambiguous | -0.13 | Destabilizing | 0.999 | D | 0.694 | prob.neutral | None | None | None | None | N |
| D/K | 0.3329 | likely_benign | 0.3267 | benign | 0.182 | Stabilizing | 0.983 | D | 0.512 | neutral | None | None | None | None | N |
| D/L | 0.3518 | ambiguous | 0.3739 | ambiguous | -0.13 | Destabilizing | 0.998 | D | 0.688 | prob.neutral | None | None | None | None | N |
| D/M | 0.4859 | ambiguous | 0.5009 | ambiguous | 0.327 | Stabilizing | 1.0 | D | 0.673 | neutral | None | None | None | None | N |
| D/N | 0.0802 | likely_benign | 0.0809 | benign | -0.163 | Destabilizing | 0.989 | D | 0.494 | neutral | N | 0.45077373 | None | None | N |
| D/P | 0.8733 | likely_pathogenic | 0.8603 | pathogenic | -0.298 | Destabilizing | 0.999 | D | 0.581 | neutral | None | None | None | None | N |
| D/Q | 0.2574 | likely_benign | 0.252 | benign | -0.14 | Destabilizing | 0.995 | D | 0.529 | neutral | None | None | None | None | N |
| D/R | 0.3871 | ambiguous | 0.3754 | ambiguous | 0.179 | Stabilizing | 0.995 | D | 0.649 | neutral | None | None | None | None | N |
| D/S | 0.1057 | likely_benign | 0.1014 | benign | -0.311 | Destabilizing | 0.983 | D | 0.427 | neutral | None | None | None | None | N |
| D/T | 0.145 | likely_benign | 0.1472 | benign | -0.12 | Destabilizing | 0.998 | D | 0.522 | neutral | None | None | None | None | N |
| D/V | 0.2142 | likely_benign | 0.2271 | benign | -0.298 | Destabilizing | 0.997 | D | 0.683 | prob.neutral | N | 0.509440627 | None | None | N |
| D/W | 0.8221 | likely_pathogenic | 0.8422 | pathogenic | -0.503 | Destabilizing | 1.0 | D | 0.674 | neutral | None | None | None | None | N |
| D/Y | 0.1764 | likely_benign | 0.1916 | benign | -0.431 | Destabilizing | 1.0 | D | 0.683 | prob.neutral | N | 0.486309942 | 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.