Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 33401 | 100426;100427;100428 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| N2AB | 31760 | 95503;95504;95505 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| N2A | 30833 | 92722;92723;92724 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| N2B | 24336 | 73231;73232;73233 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| Novex-1 | 24461 | 73606;73607;73608 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| Novex-2 | 24528 | 73807;73808;73809 | chr2:178536546;178536545;178536544 | chr2:179401273;179401272;179401271 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs748467010  |
-1.203 | 0.722 | N | 0.592 | 0.214 | 0.660803965989 | gnomAD-2.1.1 | 5.87E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 2.6096E-04 |
| I/T | rs748467010 |
-1.203 | 0.722 | N | 0.592 | 0.214 | 0.660803965989 | gnomAD-4.0.0 | 1.90502E-06 | None | None | None | None | N | None | 0 | 0 | None | 6.74946E-05 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs786205294 |
-0.687 | 0.003 | N | 0.215 | 0.111 | 0.447609009685 | gnomAD-2.1.1 | 5.89E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.18E-05 | 0 |
| I/V | rs786205294 |
-0.687 | 0.003 | N | 0.215 | 0.111 | 0.447609009685 | gnomAD-4.0.0 | 3.81537E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 6.57748E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3816 | ambiguous | 0.3733 | ambiguous | -1.873 | Destabilizing | 0.011 | N | 0.35 | neutral | None | None | None | None | N |
| I/C | 0.7273 | likely_pathogenic | 0.7109 | pathogenic | -1.233 | Destabilizing | 0.989 | D | 0.657 | neutral | None | None | None | None | N |
| I/D | 0.9342 | likely_pathogenic | 0.951 | pathogenic | -1.266 | Destabilizing | 0.961 | D | 0.743 | deleterious | None | None | None | None | N |
| I/E | 0.8833 | likely_pathogenic | 0.9034 | pathogenic | -1.216 | Destabilizing | 0.923 | D | 0.731 | prob.delet. | None | None | None | None | N |
| I/F | 0.3536 | ambiguous | 0.385 | ambiguous | -1.236 | Destabilizing | 0.901 | D | 0.603 | neutral | N | 0.504992216 | None | None | N |
| I/G | 0.8037 | likely_pathogenic | 0.8305 | pathogenic | -2.261 | Highly Destabilizing | 0.858 | D | 0.699 | prob.neutral | None | None | None | None | N |
| I/H | 0.8665 | likely_pathogenic | 0.8882 | pathogenic | -1.5 | Destabilizing | 0.996 | D | 0.716 | prob.delet. | None | None | None | None | N |
| I/K | 0.7928 | likely_pathogenic | 0.8378 | pathogenic | -1.341 | Destabilizing | 0.923 | D | 0.732 | prob.delet. | None | None | None | None | N |
| I/L | 0.2159 | likely_benign | 0.1989 | benign | -0.853 | Destabilizing | 0.19 | N | 0.422 | neutral | N | 0.445175909 | None | None | N |
| I/M | 0.1997 | likely_benign | 0.1894 | benign | -0.692 | Destabilizing | 0.901 | D | 0.606 | neutral | N | 0.521329893 | None | None | N |
| I/N | 0.6236 | likely_pathogenic | 0.6609 | pathogenic | -1.215 | Destabilizing | 0.949 | D | 0.749 | deleterious | N | 0.517540226 | None | None | N |
| I/P | 0.7722 | likely_pathogenic | 0.7926 | pathogenic | -1.163 | Destabilizing | 0.961 | D | 0.745 | deleterious | None | None | None | None | N |
| I/Q | 0.814 | likely_pathogenic | 0.8384 | pathogenic | -1.316 | Destabilizing | 0.961 | D | 0.75 | deleterious | None | None | None | None | N |
| I/R | 0.734 | likely_pathogenic | 0.7891 | pathogenic | -0.82 | Destabilizing | 0.961 | D | 0.75 | deleterious | None | None | None | None | N |
| I/S | 0.5229 | ambiguous | 0.5487 | ambiguous | -1.9 | Destabilizing | 0.565 | D | 0.683 | prob.neutral | N | 0.517020151 | None | None | N |
| I/T | 0.4029 | ambiguous | 0.3883 | ambiguous | -1.717 | Destabilizing | 0.722 | D | 0.592 | neutral | N | 0.51719351 | None | None | N |
| I/V | 0.0684 | likely_benign | 0.0619 | benign | -1.163 | Destabilizing | 0.003 | N | 0.215 | neutral | N | 0.395552378 | None | None | N |
| I/W | 0.9436 | likely_pathogenic | 0.9585 | pathogenic | -1.351 | Destabilizing | 0.996 | D | 0.713 | prob.delet. | None | None | None | None | N |
| I/Y | 0.7809 | likely_pathogenic | 0.8254 | pathogenic | -1.122 | Destabilizing | 0.961 | D | 0.668 | 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.