Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18421 | 55486;55487;55488 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| N2AB | 16780 | 50563;50564;50565 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| N2A | 15853 | 47782;47783;47784 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| N2B | 9356 | 28291;28292;28293 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| Novex-1 | 9481 | 28666;28667;28668 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| Novex-2 | 9548 | 28867;28868;28869 | chr2:178602010;178602009;178602008 | chr2:179466737;179466736;179466735 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/P | None | None | 0.602 | N | 0.392 | 0.224 | 0.273070737957 | 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 |
| A/V | rs1277409025  |
-0.615 | 0.001 | N | 0.235 | 0.118 | 0.313210971179 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| A/V | rs1277409025 |
-0.615 | 0.001 | N | 0.235 | 0.118 | 0.313210971179 | gnomAD-4.0.0 | 3.18696E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.72472E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.3296 | likely_benign | 0.2594 | benign | -0.724 | Destabilizing | 0.883 | D | 0.381 | neutral | None | None | None | None | N |
| A/D | 0.1911 | likely_benign | 0.1999 | benign | -1.546 | Destabilizing | 0.124 | N | 0.382 | neutral | None | None | None | None | N |
| A/E | 0.1571 | likely_benign | 0.1565 | benign | -1.64 | Destabilizing | None | N | 0.179 | neutral | N | 0.37613519 | None | None | N |
| A/F | 0.2384 | likely_benign | 0.1872 | benign | -1.227 | Destabilizing | 0.497 | N | 0.439 | neutral | None | None | None | None | N |
| A/G | 0.1066 | likely_benign | 0.1068 | benign | -1.119 | Destabilizing | 0.175 | N | 0.269 | neutral | N | 0.46897078 | None | None | N |
| A/H | 0.2961 | likely_benign | 0.2489 | benign | -1.306 | Destabilizing | 0.002 | N | 0.339 | neutral | None | None | None | None | N |
| A/I | 0.1377 | likely_benign | 0.1042 | benign | -0.585 | Destabilizing | 0.124 | N | 0.371 | neutral | None | None | None | None | N |
| A/K | 0.2433 | likely_benign | 0.2248 | benign | -1.335 | Destabilizing | 0.124 | N | 0.339 | neutral | None | None | None | None | N |
| A/L | 0.1273 | likely_benign | 0.1023 | benign | -0.585 | Destabilizing | 0.055 | N | 0.34 | neutral | None | None | None | None | N |
| A/M | 0.145 | likely_benign | 0.1188 | benign | -0.263 | Destabilizing | 0.667 | D | 0.379 | neutral | None | None | None | None | N |
| A/N | 0.1477 | likely_benign | 0.1354 | benign | -0.892 | Destabilizing | 0.22 | N | 0.387 | neutral | None | None | None | None | N |
| A/P | 0.2671 | likely_benign | 0.3374 | benign | -0.663 | Destabilizing | 0.602 | D | 0.392 | neutral | N | 0.43048975 | None | None | N |
| A/Q | 0.1985 | likely_benign | 0.1745 | benign | -1.172 | Destabilizing | 0.025 | N | 0.227 | neutral | None | None | None | None | N |
| A/R | 0.274 | likely_benign | 0.2461 | benign | -0.818 | Destabilizing | 0.22 | N | 0.362 | neutral | None | None | None | None | N |
| A/S | 0.0843 | likely_benign | 0.0806 | benign | -1.101 | Destabilizing | 0.042 | N | 0.313 | neutral | N | 0.442434753 | None | None | N |
| A/T | 0.0675 | likely_benign | 0.0642 | benign | -1.131 | Destabilizing | None | N | 0.119 | neutral | N | 0.419715396 | None | None | N |
| A/V | 0.0826 | likely_benign | 0.0712 | benign | -0.663 | Destabilizing | 0.001 | N | 0.235 | neutral | N | 0.498157537 | None | None | N |
| A/W | 0.5675 | likely_pathogenic | 0.5047 | ambiguous | -1.496 | Destabilizing | 0.958 | D | 0.511 | neutral | None | None | None | None | N |
| A/Y | 0.3252 | likely_benign | 0.2671 | benign | -1.173 | Destabilizing | 0.497 | N | 0.429 | 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.