Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30864 | 92815;92816;92817 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| N2AB | 29223 | 87892;87893;87894 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| N2A | 28296 | 85111;85112;85113 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| N2B | 21799 | 65620;65621;65622 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| Novex-1 | 21924 | 65995;65996;65997 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| Novex-2 | 21991 | 66196;66197;66198 | chr2:178549036;178549035;178549034 | chr2:179413763;179413762;179413761 |
| 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/N | rs200621611  |
0.275 | 0.873 | N | 0.384 | 0.138 | None | gnomAD-2.1.1 | 8.57E-05 | None | None | None | None | N | None | 0 | 8.49E-05 | None | 0 | 1.02596E-04 | None | 9.8E-05 | None | 1.19923E-04 | 9.38E-05 | 1.40371E-04 |
| D/N | rs200621611 |
0.275 | 0.873 | N | 0.384 | 0.138 | None | gnomAD-3.1.2 | 5.91E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 1.88573E-04 | 0 | 7.35E-05 | 0 | 0 |
| D/N | rs200621611 |
0.275 | 0.873 | N | 0.384 | 0.138 | None | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| D/N | rs200621611 |
0.275 | 0.873 | N | 0.384 | 0.138 | None | gnomAD-4.0.0 | 6.87782E-05 | None | None | None | None | N | None | 2.66539E-05 | 6.666E-05 | None | 3.37815E-05 | 6.68777E-05 | None | 1.40616E-04 | 0 | 7.28914E-05 | 4.39155E-05 | 3.20092E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| D/A | 0.1221 | likely_benign | 0.119 | benign | 0.029 | Stabilizing | 0.201 | N | 0.369 | neutral | N | 0.459056778 | None | None | N |
| D/C | 0.5039 | ambiguous | 0.4831 | ambiguous | -0.055 | Destabilizing | 0.992 | D | 0.381 | neutral | None | None | None | None | N |
| D/E | 0.1208 | likely_benign | 0.1227 | benign | -0.283 | Destabilizing | 0.004 | N | 0.315 | neutral | N | 0.442567173 | None | None | N |
| D/F | 0.4952 | ambiguous | 0.4879 | ambiguous | -0.054 | Destabilizing | 0.972 | D | 0.355 | neutral | None | None | None | None | N |
| D/G | 0.1159 | likely_benign | 0.1112 | benign | -0.09 | Destabilizing | 0.002 | N | 0.311 | neutral | N | 0.389962052 | None | None | N |
| D/H | 0.207 | likely_benign | 0.1971 | benign | 0.501 | Stabilizing | 0.957 | D | 0.343 | neutral | N | 0.45901025 | None | None | N |
| D/I | 0.2778 | likely_benign | 0.2661 | benign | 0.273 | Stabilizing | 0.92 | D | 0.378 | neutral | None | None | None | None | N |
| D/K | 0.289 | likely_benign | 0.2712 | benign | 0.493 | Stabilizing | 0.447 | N | 0.362 | neutral | None | None | None | None | N |
| D/L | 0.3109 | likely_benign | 0.3034 | benign | 0.273 | Stabilizing | 0.85 | D | 0.375 | neutral | None | None | None | None | N |
| D/M | 0.4869 | ambiguous | 0.4878 | ambiguous | 0.117 | Stabilizing | 0.992 | D | 0.355 | neutral | None | None | None | None | N |
| D/N | 0.0836 | likely_benign | 0.0796 | benign | 0.246 | Stabilizing | 0.873 | D | 0.384 | neutral | N | 0.46082486 | None | None | N |
| D/P | 0.5055 | ambiguous | 0.488 | ambiguous | 0.211 | Stabilizing | 0.92 | D | 0.369 | neutral | None | None | None | None | N |
| D/Q | 0.2529 | likely_benign | 0.2482 | benign | 0.247 | Stabilizing | 0.739 | D | 0.317 | neutral | None | None | None | None | N |
| D/R | 0.3353 | likely_benign | 0.3161 | benign | 0.702 | Stabilizing | 0.85 | D | 0.395 | neutral | None | None | None | None | N |
| D/S | 0.0877 | likely_benign | 0.087 | benign | 0.154 | Stabilizing | 0.026 | N | 0.209 | neutral | None | None | None | None | N |
| D/T | 0.1607 | likely_benign | 0.1601 | benign | 0.252 | Stabilizing | 0.447 | N | 0.366 | neutral | None | None | None | None | N |
| D/V | 0.1694 | likely_benign | 0.1635 | benign | 0.211 | Stabilizing | 0.81 | D | 0.379 | neutral | N | 0.506696009 | None | None | N |
| D/W | 0.8149 | likely_pathogenic | 0.8104 | pathogenic | -0.009 | Destabilizing | 0.992 | D | 0.474 | neutral | None | None | None | None | N |
| D/Y | 0.2221 | likely_benign | 0.2046 | benign | 0.176 | Stabilizing | 0.985 | D | 0.353 | neutral | N | 0.464290169 | 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.