Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22894 | 68905;68906;68907 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| N2AB | 21253 | 63982;63983;63984 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| N2A | 20326 | 61201;61202;61203 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| N2B | 13829 | 41710;41711;41712 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| Novex-1 | 13954 | 42085;42086;42087 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| Novex-2 | 14021 | 42286;42287;42288 | chr2:178577746;178577745;178577744 | chr2:179442473;179442472;179442471 |
| 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/D | rs2046759146  |
None | 0.949 | N | 0.623 | 0.358 | 0.545130385147 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/D | rs2046759146 |
None | 0.949 | N | 0.623 | 0.358 | 0.545130385147 | gnomAD-4.0.0 | 6.57471E-06 | None | None | None | None | I | None | 2.41371E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 | 0.2174 | likely_benign | 0.2712 | benign | -0.532 | Destabilizing | 0.517 | D | 0.365 | neutral | N | 0.464185744 | None | None | I |
| V/C | 0.6717 | likely_pathogenic | 0.7168 | pathogenic | -0.697 | Destabilizing | 0.996 | D | 0.476 | neutral | None | None | None | None | I |
| V/D | 0.4454 | ambiguous | 0.5299 | ambiguous | -0.349 | Destabilizing | 0.949 | D | 0.623 | neutral | N | 0.502146699 | None | None | I |
| V/E | 0.3855 | ambiguous | 0.4672 | ambiguous | -0.434 | Destabilizing | 0.961 | D | 0.561 | neutral | None | None | None | None | I |
| V/F | 0.2017 | likely_benign | 0.2411 | benign | -0.676 | Destabilizing | 0.901 | D | 0.429 | neutral | N | 0.468531174 | None | None | I |
| V/G | 0.2469 | likely_benign | 0.2895 | benign | -0.677 | Destabilizing | 0.949 | D | 0.605 | neutral | N | 0.468380842 | None | None | I |
| V/H | 0.6038 | likely_pathogenic | 0.6762 | pathogenic | -0.159 | Destabilizing | 0.996 | D | 0.628 | neutral | None | None | None | None | I |
| V/I | 0.0749 | likely_benign | 0.0763 | benign | -0.282 | Destabilizing | 0.008 | N | 0.213 | neutral | N | 0.49419922 | None | None | I |
| V/K | 0.4369 | ambiguous | 0.5189 | ambiguous | -0.486 | Destabilizing | 0.961 | D | 0.557 | neutral | None | None | None | None | I |
| V/L | 0.2028 | likely_benign | 0.2322 | benign | -0.282 | Destabilizing | 0.156 | N | 0.333 | neutral | N | 0.514054417 | None | None | I |
| V/M | 0.1505 | likely_benign | 0.1643 | benign | -0.491 | Destabilizing | 0.923 | D | 0.384 | neutral | None | None | None | None | I |
| V/N | 0.2736 | likely_benign | 0.3153 | benign | -0.285 | Destabilizing | 0.961 | D | 0.623 | neutral | None | None | None | None | I |
| V/P | 0.827 | likely_pathogenic | 0.8578 | pathogenic | -0.332 | Destabilizing | 0.987 | D | 0.563 | neutral | None | None | None | None | I |
| V/Q | 0.3608 | ambiguous | 0.4293 | ambiguous | -0.472 | Destabilizing | 0.987 | D | 0.566 | neutral | None | None | None | None | I |
| V/R | 0.3988 | ambiguous | 0.4818 | ambiguous | -0.003 | Destabilizing | 0.961 | D | 0.627 | neutral | None | None | None | None | I |
| V/S | 0.2396 | likely_benign | 0.2807 | benign | -0.647 | Destabilizing | 0.858 | D | 0.439 | neutral | None | None | None | None | I |
| V/T | 0.1876 | likely_benign | 0.2234 | benign | -0.624 | Destabilizing | 0.096 | N | 0.201 | neutral | None | None | None | None | I |
| V/W | 0.814 | likely_pathogenic | 0.875 | pathogenic | -0.763 | Destabilizing | 0.996 | D | 0.641 | neutral | None | None | None | None | I |
| V/Y | 0.5378 | ambiguous | 0.6364 | pathogenic | -0.473 | Destabilizing | 0.961 | D | 0.441 | 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.