Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 9283 | 28072;28073;28074 | chr2:178711983;178711982;178711981 | chr2:179576710;179576709;179576708 |
| N2AB | 8966 | 27121;27122;27123 | chr2:178711983;178711982;178711981 | chr2:179576710;179576709;179576708 |
| N2A | 8039 | 24340;24341;24342 | chr2:178711983;178711982;178711981 | chr2:179576710;179576709;179576708 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 | rs727504515  |
-0.304 | 0.999 | D | 0.568 | 0.334 | 0.419713421852 | gnomAD-2.1.1 | 1.66155E-04 | None | None | None | None | I | None | 0 | 6.99545E-04 | None | 0 | 5.57E-05 | None | 4.64807E-04 | None | 0 | 1.79E-05 | 0 |
| V/M | rs727504515 |
-0.304 | 0.999 | D | 0.568 | 0.334 | 0.419713421852 | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | I | None | 2.41E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 4.41E-05 | 1.03605E-03 | 0 |
| V/M | rs727504515 |
-0.304 | 0.999 | D | 0.568 | 0.334 | 0.419713421852 | gnomAD-4.0.0 | 8.32842E-05 | None | None | None | None | I | None | 5.34559E-05 | 4.18018E-04 | None | 0 | 2.23155E-04 | None | 0 | 0 | 1.69993E-05 | 7.96901E-04 | 4.8185E-05 |
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 | 0.174 | likely_benign | 0.2266 | benign | -0.35 | Destabilizing | 0.948 | D | 0.513 | neutral | N | 0.432567263 | None | None | I |
| V/C | 0.8513 | likely_pathogenic | 0.8435 | pathogenic | -0.84 | Destabilizing | 1.0 | D | 0.586 | neutral | None | None | None | None | I |
| V/D | 0.8581 | likely_pathogenic | 0.8679 | pathogenic | -0.242 | Destabilizing | 0.999 | D | 0.671 | neutral | None | None | None | None | I |
| V/E | 0.7148 | likely_pathogenic | 0.7332 | pathogenic | -0.36 | Destabilizing | 0.999 | D | 0.633 | neutral | N | 0.488089548 | None | None | I |
| V/F | 0.2385 | likely_benign | 0.2707 | benign | -0.706 | Destabilizing | 0.998 | D | 0.571 | neutral | None | None | None | None | I |
| V/G | 0.4876 | ambiguous | 0.5325 | ambiguous | -0.405 | Destabilizing | 0.999 | D | 0.654 | neutral | D | 0.532963544 | None | None | I |
| V/H | 0.8302 | likely_pathogenic | 0.8386 | pathogenic | -0.002 | Destabilizing | 1.0 | D | 0.68 | prob.neutral | None | None | None | None | I |
| V/I | 0.0822 | likely_benign | 0.0869 | benign | -0.348 | Destabilizing | 0.246 | N | 0.305 | neutral | None | None | None | None | I |
| V/K | 0.7356 | likely_pathogenic | 0.7365 | pathogenic | -0.355 | Destabilizing | 0.999 | D | 0.636 | neutral | None | None | None | None | I |
| V/L | 0.381 | ambiguous | 0.4116 | ambiguous | -0.348 | Destabilizing | 0.958 | D | 0.463 | neutral | N | 0.495117231 | None | None | I |
| V/M | 0.2402 | likely_benign | 0.2853 | benign | -0.542 | Destabilizing | 0.999 | D | 0.568 | neutral | D | 0.537158642 | None | None | I |
| V/N | 0.6957 | likely_pathogenic | 0.7105 | pathogenic | -0.197 | Destabilizing | 0.999 | D | 0.669 | neutral | None | None | None | None | I |
| V/P | 0.9546 | likely_pathogenic | 0.9707 | pathogenic | -0.321 | Destabilizing | 0.999 | D | 0.635 | neutral | None | None | None | None | I |
| V/Q | 0.6857 | likely_pathogenic | 0.6982 | pathogenic | -0.405 | Destabilizing | 0.999 | D | 0.637 | neutral | None | None | None | None | I |
| V/R | 0.609 | likely_pathogenic | 0.6181 | pathogenic | 0.089 | Stabilizing | 0.999 | D | 0.663 | neutral | None | None | None | None | I |
| V/S | 0.3736 | ambiguous | 0.4138 | ambiguous | -0.525 | Destabilizing | 0.999 | D | 0.592 | neutral | None | None | None | None | I |
| V/T | 0.2598 | likely_benign | 0.3085 | benign | -0.55 | Destabilizing | 0.992 | D | 0.513 | neutral | None | None | None | None | I |
| V/W | 0.9082 | likely_pathogenic | 0.9294 | pathogenic | -0.754 | Destabilizing | 1.0 | D | 0.713 | prob.delet. | None | None | None | None | I |
| V/Y | 0.7713 | likely_pathogenic | 0.7862 | pathogenic | -0.483 | Destabilizing | 0.999 | D | 0.564 | neutral | None | None | None | None | I |
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.