Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22993 | 69202;69203;69204 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| N2AB | 21352 | 64279;64280;64281 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| N2A | 20425 | 61498;61499;61500 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| N2B | 13928 | 42007;42008;42009 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| Novex-1 | 14053 | 42382;42383;42384 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| Novex-2 | 14120 | 42583;42584;42585 | chr2:178577358;178577357;178577356 | chr2:179442085;179442084;179442083 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/T | rs2046666627  |
None | 0.001 | N | 0.195 | 0.058 | 0.407767136052 | gnomAD-3.1.2 | 6.6E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 2.08681E-04 | 0 |
| I/T | rs2046666627 |
None | 0.001 | N | 0.195 | 0.058 | 0.407767136052 | gnomAD-4.0.0 | 6.5977E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 2.08681E-04 | 0 |
| I/V | rs752579029 |
-0.796 | 0.001 | N | 0.109 | 0.047 | 0.339555952218 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/V | rs752579029 |
-0.796 | 0.001 | N | 0.109 | 0.047 | 0.339555952218 | gnomAD-4.0.0 | 1.59204E-06 | None | None | None | None | N | None | 0 | 2.28697E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1947 | likely_benign | 0.1859 | benign | -1.033 | Destabilizing | 0.116 | N | 0.281 | neutral | None | None | None | None | N |
| I/C | 0.5453 | ambiguous | 0.5194 | ambiguous | -0.743 | Destabilizing | 0.944 | D | 0.36 | neutral | None | None | None | None | N |
| I/D | 0.4523 | ambiguous | 0.4309 | ambiguous | -0.221 | Destabilizing | 0.69 | D | 0.437 | neutral | None | None | None | None | N |
| I/E | 0.4032 | ambiguous | 0.3734 | ambiguous | -0.272 | Destabilizing | 0.69 | D | 0.439 | neutral | None | None | None | None | N |
| I/F | 0.1262 | likely_benign | 0.1169 | benign | -0.8 | Destabilizing | 0.627 | D | 0.347 | neutral | N | 0.458920705 | None | None | N |
| I/G | 0.4217 | ambiguous | 0.3986 | ambiguous | -1.274 | Destabilizing | 0.69 | D | 0.441 | neutral | None | None | None | None | N |
| I/H | 0.3236 | likely_benign | 0.3054 | benign | -0.496 | Destabilizing | 0.981 | D | 0.443 | neutral | None | None | None | None | N |
| I/K | 0.2143 | likely_benign | 0.1877 | benign | -0.573 | Destabilizing | 0.69 | D | 0.435 | neutral | None | None | None | None | N |
| I/L | 0.0977 | likely_benign | 0.0999 | benign | -0.492 | Destabilizing | 0.001 | N | 0.079 | neutral | N | 0.439814869 | None | None | N |
| I/M | 0.0837 | likely_benign | 0.0837 | benign | -0.443 | Destabilizing | 0.627 | D | 0.381 | neutral | N | 0.474178159 | None | None | N |
| I/N | 0.1284 | likely_benign | 0.1313 | benign | -0.344 | Destabilizing | 0.627 | D | 0.435 | neutral | N | 0.390367484 | None | None | N |
| I/P | 0.7338 | likely_pathogenic | 0.7259 | pathogenic | -0.638 | Destabilizing | 0.818 | D | 0.439 | neutral | None | None | None | None | N |
| I/Q | 0.2932 | likely_benign | 0.2733 | benign | -0.54 | Destabilizing | 0.818 | D | 0.426 | neutral | None | None | None | None | N |
| I/R | 0.1851 | likely_benign | 0.1654 | benign | -0.021 | Destabilizing | 0.69 | D | 0.435 | neutral | None | None | None | None | N |
| I/S | 0.1682 | likely_benign | 0.168 | benign | -0.925 | Destabilizing | 0.193 | N | 0.374 | neutral | N | 0.417284726 | None | None | N |
| I/T | 0.1241 | likely_benign | 0.1278 | benign | -0.857 | Destabilizing | 0.001 | N | 0.195 | neutral | N | 0.443681894 | None | None | N |
| I/V | 0.0715 | likely_benign | 0.0671 | benign | -0.638 | Destabilizing | 0.001 | N | 0.109 | neutral | N | 0.439988228 | None | None | N |
| I/W | 0.6985 | likely_pathogenic | 0.6883 | pathogenic | -0.807 | Destabilizing | 0.981 | D | 0.547 | neutral | None | None | None | None | N |
| I/Y | 0.366 | ambiguous | 0.3436 | ambiguous | -0.575 | Destabilizing | 0.818 | D | 0.366 | 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.