Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27340 | 82243;82244;82245 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| N2AB | 25699 | 77320;77321;77322 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| N2A | 24772 | 74539;74540;74541 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| N2B | 18275 | 55048;55049;55050 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| Novex-1 | 18400 | 55423;55424;55425 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| Novex-2 | 18467 | 55624;55625;55626 | chr2:178564114;178564113;178564112 | chr2:179428841;179428840;179428839 |
| 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/K | rs371592971  |
-0.144 | 0.879 | N | 0.659 | 0.295 | 0.72687828099 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 8.69E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/K | rs371592971 |
-0.144 | 0.879 | N | 0.659 | 0.295 | 0.72687828099 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 2.41E-05 | 1.31079E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 4.78469E-04 |
| I/K | rs371592971 |
-0.144 | 0.879 | N | 0.659 | 0.295 | 0.72687828099 | gnomAD-4.0.0 | 8.67598E-06 | None | None | None | None | I | None | 1.33494E-05 | 1.16702E-04 | None | 0 | 0 | None | 0 | 0 | 8.47642E-07 | 0 | 8.00615E-05 |
| I/T | rs371592971 |
None | 0.338 | N | 0.545 | 0.188 | None | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/T | rs371592971 |
None | 0.338 | N | 0.545 | 0.188 | None | gnomAD-4.0.0 | 4.9577E-06 | None | None | None | None | I | None | 0 | 1.66717E-05 | None | 0 | 0 | None | 0 | 0 | 5.93349E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.196 | likely_benign | 0.2063 | benign | -1.397 | Destabilizing | 0.218 | N | 0.512 | neutral | None | None | None | None | I |
| I/C | 0.4723 | ambiguous | 0.4943 | ambiguous | -0.745 | Destabilizing | 0.973 | D | 0.614 | neutral | None | None | None | None | I |
| I/D | 0.4404 | ambiguous | 0.4733 | ambiguous | -0.979 | Destabilizing | 0.906 | D | 0.682 | prob.neutral | None | None | None | None | I |
| I/E | 0.3435 | ambiguous | 0.3757 | ambiguous | -1.049 | Destabilizing | 0.906 | D | 0.659 | neutral | None | None | None | None | I |
| I/F | 0.1258 | likely_benign | 0.1328 | benign | -1.257 | Destabilizing | 0.826 | D | 0.519 | neutral | None | None | None | None | I |
| I/G | 0.3357 | likely_benign | 0.3622 | ambiguous | -1.639 | Destabilizing | 0.906 | D | 0.635 | neutral | None | None | None | None | I |
| I/H | 0.2934 | likely_benign | 0.3233 | benign | -0.86 | Destabilizing | 0.991 | D | 0.701 | prob.neutral | None | None | None | None | I |
| I/K | 0.1883 | likely_benign | 0.2292 | benign | -0.848 | Destabilizing | 0.879 | D | 0.659 | neutral | N | 0.45276639 | None | None | I |
| I/L | 0.0806 | likely_benign | 0.0833 | benign | -0.841 | Destabilizing | 0.084 | N | 0.301 | neutral | N | 0.49388508 | None | None | I |
| I/M | 0.0881 | likely_benign | 0.0898 | benign | -0.476 | Destabilizing | 0.174 | N | 0.395 | neutral | N | 0.497829463 | None | None | I |
| I/N | 0.1361 | likely_benign | 0.1495 | benign | -0.579 | Destabilizing | 0.967 | D | 0.696 | prob.neutral | None | None | None | None | I |
| I/P | 0.7684 | likely_pathogenic | 0.7708 | pathogenic | -0.994 | Destabilizing | 0.967 | D | 0.685 | prob.neutral | None | None | None | None | I |
| I/Q | 0.2224 | likely_benign | 0.2499 | benign | -0.875 | Destabilizing | 0.906 | D | 0.698 | prob.neutral | None | None | None | None | I |
| I/R | 0.1544 | likely_benign | 0.1843 | benign | -0.151 | Destabilizing | 0.879 | D | 0.69 | prob.neutral | N | 0.434932777 | None | None | I |
| I/S | 0.138 | likely_benign | 0.1523 | benign | -1.104 | Destabilizing | 0.826 | D | 0.545 | neutral | None | None | None | None | I |
| I/T | 0.1225 | likely_benign | 0.1296 | benign | -1.069 | Destabilizing | 0.338 | N | 0.545 | neutral | N | 0.439530521 | None | None | I |
| I/V | 0.0635 | likely_benign | 0.0618 | benign | -0.994 | Destabilizing | 0.001 | N | 0.166 | neutral | N | 0.43758908 | None | None | I |
| I/W | 0.6898 | likely_pathogenic | 0.7179 | pathogenic | -1.262 | Destabilizing | 0.991 | D | 0.763 | deleterious | None | None | None | None | I |
| I/Y | 0.4067 | ambiguous | 0.4303 | ambiguous | -1.038 | Destabilizing | 0.906 | D | 0.615 | neutral | None | None | None | None | I |
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.