Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20529 | 61810;61811;61812 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| N2AB | 18888 | 56887;56888;56889 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| N2A | 17961 | 54106;54107;54108 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| N2B | 11464 | 34615;34616;34617 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| Novex-1 | 11589 | 34990;34991;34992 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| Novex-2 | 11656 | 35191;35192;35193 | chr2:178590140;178590139;178590138 | chr2:179454867;179454866;179454865 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/I | None | None | 0.811 | N | 0.277 | 0.111 | 0.451407941134 | gnomAD-4.0.0 | 6.84432E-07 | None | None | None | None | N | None | 0 | 2.23754E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs777103102  |
0.027 | 0.995 | N | 0.475 | 0.434 | 0.473695954338 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | N | None | 0 | 8.71E-05 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 0 |
| L/P | rs777103102 |
0.027 | 0.995 | N | 0.475 | 0.434 | 0.473695954338 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | N | None | 4.83E-05 | 6.55E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/P | rs777103102 |
0.027 | 0.995 | N | 0.475 | 0.434 | 0.473695954338 | gnomAD-4.0.0 | 1.02561E-05 | None | None | None | None | N | None | 3.38467E-05 | 8.4786E-05 | None | 0 | 0 | None | 0 | 0 | 2.39469E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.2528 | likely_benign | 0.2603 | benign | -1.569 | Destabilizing | 0.959 | D | 0.284 | neutral | None | None | None | None | N |
| L/C | 0.4619 | ambiguous | 0.514 | ambiguous | -0.977 | Destabilizing | 0.999 | D | 0.346 | neutral | None | None | None | None | N |
| L/D | 0.6146 | likely_pathogenic | 0.6338 | pathogenic | -1.203 | Destabilizing | 0.996 | D | 0.478 | neutral | None | None | None | None | N |
| L/E | 0.4094 | ambiguous | 0.4316 | ambiguous | -1.195 | Destabilizing | 0.996 | D | 0.479 | neutral | None | None | None | None | N |
| L/F | 0.0981 | likely_benign | 0.1029 | benign | -1.06 | Destabilizing | 0.015 | N | 0.141 | neutral | None | None | None | None | N |
| L/G | 0.423 | ambiguous | 0.4465 | ambiguous | -1.893 | Destabilizing | 0.988 | D | 0.473 | neutral | None | None | None | None | N |
| L/H | 0.2048 | likely_benign | 0.2347 | benign | -1.136 | Destabilizing | 0.999 | D | 0.486 | neutral | None | None | None | None | N |
| L/I | 0.0853 | likely_benign | 0.0852 | benign | -0.753 | Destabilizing | 0.811 | D | 0.277 | neutral | N | 0.398584322 | None | None | N |
| L/K | 0.2949 | likely_benign | 0.3232 | benign | -1.264 | Destabilizing | 0.996 | D | 0.419 | neutral | None | None | None | None | N |
| L/M | 0.1187 | likely_benign | 0.1132 | benign | -0.626 | Destabilizing | 0.988 | D | 0.261 | neutral | None | None | None | None | N |
| L/N | 0.2938 | likely_benign | 0.304 | benign | -1.085 | Destabilizing | 0.996 | D | 0.484 | neutral | None | None | None | None | N |
| L/P | 0.2215 | likely_benign | 0.2504 | benign | -0.994 | Destabilizing | 0.995 | D | 0.475 | neutral | N | 0.404643503 | None | None | N |
| L/Q | 0.1957 | likely_benign | 0.2121 | benign | -1.234 | Destabilizing | 0.995 | D | 0.415 | neutral | N | 0.433715616 | None | None | N |
| L/R | 0.2551 | likely_benign | 0.3059 | benign | -0.67 | Destabilizing | 0.995 | D | 0.418 | neutral | N | 0.431118028 | None | None | N |
| L/S | 0.2325 | likely_benign | 0.2645 | benign | -1.628 | Destabilizing | 0.988 | D | 0.365 | neutral | None | None | None | None | N |
| L/T | 0.2098 | likely_benign | 0.2157 | benign | -1.501 | Destabilizing | 0.988 | D | 0.244 | neutral | None | None | None | None | N |
| L/V | 0.1068 | likely_benign | 0.1062 | benign | -0.994 | Destabilizing | 0.896 | D | 0.309 | neutral | N | 0.437371997 | None | None | N |
| L/W | 0.2191 | likely_benign | 0.2552 | benign | -1.161 | Destabilizing | 0.999 | D | 0.441 | neutral | None | None | None | None | N |
| L/Y | 0.2278 | likely_benign | 0.2571 | benign | -0.947 | Destabilizing | 0.851 | D | 0.275 | 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.