Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22988 | 69187;69188;69189 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| N2AB | 21347 | 64264;64265;64266 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| N2A | 20420 | 61483;61484;61485 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| N2B | 13923 | 41992;41993;41994 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| Novex-1 | 14048 | 42367;42368;42369 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| Novex-2 | 14115 | 42568;42569;42570 | chr2:178577373;178577372;178577371 | chr2:179442100;179442099;179442098 |
| 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/M | rs777786229  |
-0.824 | 0.427 | N | 0.463 | 0.132 | 0.466486631293 | gnomAD-2.1.1 | 3.22E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 4.48029E-04 | None | 0 | None | 0 | 0 | 0 |
| I/M | rs777786229 |
-0.824 | 0.427 | N | 0.463 | 0.132 | 0.466486631293 | gnomAD-4.0.0 | 9.55317E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.66778E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/N | None | None | 0.001 | N | 0.397 | 0.439 | 0.784817505192 | gnomAD-4.0.0 | 1.59217E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.77948E-05 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs2046671312 |
None | 0.081 | N | 0.353 | 0.382 | 0.703127994698 | gnomAD-4.0.0 | 1.59217E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43336E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5981 | likely_pathogenic | 0.5401 | ambiguous | -2.154 | Highly Destabilizing | 0.055 | N | 0.322 | neutral | None | None | None | None | N |
| I/C | 0.6139 | likely_pathogenic | 0.6015 | pathogenic | -1.696 | Destabilizing | 0.667 | D | 0.495 | neutral | None | None | None | None | N |
| I/D | 0.9143 | likely_pathogenic | 0.9043 | pathogenic | -1.326 | Destabilizing | 0.124 | N | 0.496 | neutral | None | None | None | None | N |
| I/E | 0.8621 | likely_pathogenic | 0.8449 | pathogenic | -1.179 | Destabilizing | 0.22 | N | 0.483 | neutral | None | None | None | None | N |
| I/F | 0.0921 | likely_benign | 0.0992 | benign | -1.293 | Destabilizing | None | N | 0.084 | neutral | N | 0.485481815 | None | None | N |
| I/G | 0.8443 | likely_pathogenic | 0.8168 | pathogenic | -2.615 | Highly Destabilizing | 0.124 | N | 0.427 | neutral | None | None | None | None | N |
| I/H | 0.7027 | likely_pathogenic | 0.6929 | pathogenic | -1.714 | Destabilizing | 0.667 | D | 0.523 | neutral | None | None | None | None | N |
| I/K | 0.7679 | likely_pathogenic | 0.7459 | pathogenic | -1.549 | Destabilizing | 0.22 | N | 0.482 | neutral | None | None | None | None | N |
| I/L | 0.0952 | likely_benign | 0.0964 | benign | -0.88 | Destabilizing | None | N | 0.077 | neutral | N | 0.454862545 | None | None | N |
| I/M | 0.1109 | likely_benign | 0.114 | benign | -0.936 | Destabilizing | 0.427 | N | 0.463 | neutral | N | 0.489041054 | None | None | N |
| I/N | 0.5854 | likely_pathogenic | 0.5839 | pathogenic | -1.645 | Destabilizing | 0.001 | N | 0.397 | neutral | N | 0.500841886 | None | None | N |
| I/P | 0.9002 | likely_pathogenic | 0.883 | pathogenic | -1.279 | Destabilizing | 0.859 | D | 0.549 | neutral | None | None | None | None | N |
| I/Q | 0.7413 | likely_pathogenic | 0.7186 | pathogenic | -1.577 | Destabilizing | 0.497 | N | 0.537 | neutral | None | None | None | None | N |
| I/R | 0.668 | likely_pathogenic | 0.6522 | pathogenic | -1.199 | Destabilizing | 0.497 | N | 0.555 | neutral | None | None | None | None | N |
| I/S | 0.5932 | likely_pathogenic | 0.5744 | pathogenic | -2.446 | Highly Destabilizing | 0.042 | N | 0.38 | neutral | D | 0.526832953 | None | None | N |
| I/T | 0.5129 | ambiguous | 0.4636 | ambiguous | -2.138 | Highly Destabilizing | 0.081 | N | 0.353 | neutral | N | 0.517461203 | None | None | N |
| I/V | 0.1023 | likely_benign | 0.0841 | benign | -1.279 | Destabilizing | None | N | 0.101 | neutral | N | 0.495002588 | None | None | N |
| I/W | 0.7077 | likely_pathogenic | 0.7333 | pathogenic | -1.381 | Destabilizing | 0.883 | D | 0.509 | neutral | None | None | None | None | N |
| I/Y | 0.4368 | ambiguous | 0.4649 | ambiguous | -1.169 | Destabilizing | 0.124 | N | 0.405 | 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.