Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22201 | 66826;66827;66828 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| N2AB | 20560 | 61903;61904;61905 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| N2A | 19633 | 59122;59123;59124 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| N2B | 13136 | 39631;39632;39633 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| Novex-1 | 13261 | 40006;40007;40008 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| Novex-2 | 13328 | 40207;40208;40209 | chr2:178581667;178581666;178581665 | chr2:179446394;179446393;179446392 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/G | None | None | 0.505 | N | 0.513 | 0.136 | 0.195762928549 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| D/N | rs368924655  |
0.528 | 0.852 | N | 0.497 | 0.21 | None | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 4.7E-05 | 0 |
| D/N | rs368924655 |
0.528 | 0.852 | N | 0.497 | 0.21 | None | gnomAD-3.1.2 | 9.21E-05 | None | None | None | None | N | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.61841E-04 | 0 | 0 |
| D/N | rs368924655 |
0.528 | 0.852 | N | 0.497 | 0.21 | None | gnomAD-4.0.0 | 3.22449E-05 | None | None | None | None | N | None | 4.00203E-05 | 0 | None | 0 | 4.4827E-05 | None | 0 | 1.65289E-04 | 3.90084E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1431 | likely_benign | 0.1521 | benign | -0.156 | Destabilizing | 0.338 | N | 0.487 | neutral | N | 0.484251585 | None | None | N |
| D/C | 0.5601 | ambiguous | 0.6012 | pathogenic | -0.016 | Destabilizing | 0.973 | D | 0.581 | neutral | None | None | None | None | N |
| D/E | 0.1137 | likely_benign | 0.1134 | benign | -0.196 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.419333315 | None | None | N |
| D/F | 0.6698 | likely_pathogenic | 0.6912 | pathogenic | -0.156 | Destabilizing | 0.826 | D | 0.58 | neutral | None | None | None | None | N |
| D/G | 0.1378 | likely_benign | 0.1501 | benign | -0.304 | Destabilizing | 0.505 | D | 0.513 | neutral | N | 0.425373853 | None | None | N |
| D/H | 0.3092 | likely_benign | 0.3471 | ambiguous | 0.259 | Stabilizing | 0.949 | D | 0.591 | neutral | N | 0.467165276 | None | None | N |
| D/I | 0.3601 | ambiguous | 0.3824 | ambiguous | 0.176 | Stabilizing | 0.45 | N | 0.497 | neutral | None | None | None | None | N |
| D/K | 0.2629 | likely_benign | 0.2943 | benign | 0.401 | Stabilizing | 0.404 | N | 0.514 | neutral | None | None | None | None | N |
| D/L | 0.3346 | likely_benign | 0.3629 | ambiguous | 0.176 | Stabilizing | 0.404 | N | 0.499 | neutral | None | None | None | None | N |
| D/M | 0.5471 | ambiguous | 0.5686 | pathogenic | 0.161 | Stabilizing | 0.947 | D | 0.581 | neutral | None | None | None | None | N |
| D/N | 0.1086 | likely_benign | 0.1133 | benign | 0.166 | Stabilizing | 0.852 | D | 0.497 | neutral | N | 0.479997771 | None | None | N |
| D/P | 0.3675 | ambiguous | 0.4155 | ambiguous | 0.085 | Stabilizing | 0.906 | D | 0.551 | neutral | None | None | None | None | N |
| D/Q | 0.2451 | likely_benign | 0.2756 | benign | 0.188 | Stabilizing | 0.704 | D | 0.508 | neutral | None | None | None | None | N |
| D/R | 0.3451 | ambiguous | 0.3832 | ambiguous | 0.605 | Stabilizing | 0.826 | D | 0.543 | neutral | None | None | None | None | N |
| D/S | 0.1115 | likely_benign | 0.1233 | benign | 0.049 | Stabilizing | 0.404 | N | 0.499 | neutral | None | None | None | None | N |
| D/T | 0.1758 | likely_benign | 0.2002 | benign | 0.172 | Stabilizing | 0.404 | N | 0.534 | neutral | None | None | None | None | N |
| D/V | 0.2088 | likely_benign | 0.2215 | benign | 0.085 | Stabilizing | 0.003 | N | 0.495 | neutral | N | 0.509301958 | None | None | N |
| D/W | 0.8576 | likely_pathogenic | 0.8788 | pathogenic | -0.059 | Destabilizing | 0.991 | D | 0.63 | neutral | None | None | None | None | N |
| D/Y | 0.3218 | likely_benign | 0.3455 | ambiguous | 0.08 | Stabilizing | 0.949 | D | 0.581 | neutral | N | 0.514401134 | 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.