Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30851 | 92776;92777;92778 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| N2AB | 29210 | 87853;87854;87855 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| N2A | 28283 | 85072;85073;85074 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| N2B | 21786 | 65581;65582;65583 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| Novex-1 | 21911 | 65956;65957;65958 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| Novex-2 | 21978 | 66157;66158;66159 | chr2:178549075;178549074;178549073 | chr2:179413802;179413801;179413800 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/I | rs1233656896  |
0.184 | 0.012 | N | 0.387 | 0.068 | 0.421920138742 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 5.57E-05 | None | 0 | None | 0 | 0 | 0 |
| M/I | rs1233656896 |
0.184 | 0.012 | N | 0.387 | 0.068 | 0.421920138742 | gnomAD-4.0.0 | 1.59113E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 2.77331E-05 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs1206527 |
1.052 | 0.055 | N | 0.623 | 0.226 | 0.458644561121 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 1.29182E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| M/R | rs1206527 |
1.052 | 0.055 | N | 0.623 | 0.226 | 0.458644561121 | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| M/R | rs1206527 |
1.052 | 0.055 | N | 0.623 | 0.226 | 0.458644561121 | gnomAD-4.0.0 | 5.57704E-06 | None | None | None | None | I | None | 1.20141E-04 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3193 | likely_benign | 0.3212 | benign | -0.801 | Destabilizing | None | N | 0.335 | neutral | None | None | None | None | I |
| M/C | 0.6112 | likely_pathogenic | 0.6216 | pathogenic | -0.703 | Destabilizing | 0.628 | D | 0.611 | neutral | None | None | None | None | I |
| M/D | 0.7982 | likely_pathogenic | 0.8034 | pathogenic | -0.134 | Destabilizing | 0.072 | N | 0.671 | neutral | None | None | None | None | I |
| M/E | 0.4774 | ambiguous | 0.4912 | ambiguous | -0.18 | Destabilizing | 0.072 | N | 0.581 | neutral | None | None | None | None | I |
| M/F | 0.4195 | ambiguous | 0.4359 | ambiguous | -0.451 | Destabilizing | 0.038 | N | 0.534 | neutral | None | None | None | None | I |
| M/G | 0.5114 | ambiguous | 0.5381 | ambiguous | -1.005 | Destabilizing | 0.016 | N | 0.583 | neutral | None | None | None | None | I |
| M/H | 0.5492 | ambiguous | 0.55 | ambiguous | -0.231 | Destabilizing | 0.356 | N | 0.634 | neutral | None | None | None | None | I |
| M/I | 0.4558 | ambiguous | 0.448 | ambiguous | -0.343 | Destabilizing | 0.012 | N | 0.387 | neutral | N | 0.4528326 | None | None | I |
| M/K | 0.2036 | likely_benign | 0.2123 | benign | 0.248 | Stabilizing | 0.012 | N | 0.533 | neutral | N | 0.428782304 | None | None | I |
| M/L | 0.0823 | likely_benign | 0.085 | benign | -0.343 | Destabilizing | None | N | 0.24 | neutral | N | 0.373545097 | None | None | I |
| M/N | 0.4944 | ambiguous | 0.4907 | ambiguous | 0.397 | Stabilizing | 0.038 | N | 0.681 | prob.neutral | None | None | None | None | I |
| M/P | 0.9162 | likely_pathogenic | 0.9382 | pathogenic | -0.467 | Destabilizing | 0.136 | N | 0.663 | neutral | None | None | None | None | I |
| M/Q | 0.2413 | likely_benign | 0.2432 | benign | 0.183 | Stabilizing | 0.072 | N | 0.585 | neutral | None | None | None | None | I |
| M/R | 0.2217 | likely_benign | 0.2464 | benign | 0.722 | Stabilizing | 0.055 | N | 0.623 | neutral | N | 0.396765886 | None | None | I |
| M/S | 0.3413 | ambiguous | 0.3584 | ambiguous | -0.076 | Destabilizing | None | N | 0.365 | neutral | None | None | None | None | I |
| M/T | 0.1929 | likely_benign | 0.2194 | benign | -0.022 | Destabilizing | 0.012 | N | 0.5 | neutral | N | 0.3966326 | None | None | I |
| M/V | 0.1517 | likely_benign | 0.148 | benign | -0.467 | Destabilizing | 0.005 | N | 0.364 | neutral | N | 0.426454075 | None | None | I |
| M/W | 0.6449 | likely_pathogenic | 0.6551 | pathogenic | -0.395 | Destabilizing | 0.864 | D | 0.603 | neutral | None | None | None | None | I |
| M/Y | 0.6248 | likely_pathogenic | 0.613 | pathogenic | -0.246 | Destabilizing | 0.356 | N | 0.637 | 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.