Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17905 | 53938;53939;53940 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| N2AB | 16264 | 49015;49016;49017 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| N2A | 15337 | 46234;46235;46236 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| N2B | 8840 | 26743;26744;26745 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| Novex-1 | 8965 | 27118;27119;27120 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| Novex-2 | 9032 | 27319;27320;27321 | chr2:178605582;178605581;178605580 | chr2:179470309;179470308;179470307 |
| 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/E | rs1366977449  |
0.036 | 1.0 | N | 0.402 | 0.246 | 0.291694819147 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 6.49E-05 | 0 |
| D/E | rs1366977449 |
0.036 | 1.0 | N | 0.402 | 0.246 | 0.291694819147 | gnomAD-3.1.2 | 6.67E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.48E-05 | 0 | 0 |
| D/E | rs1366977449 |
0.036 | 1.0 | N | 0.402 | 0.246 | 0.291694819147 | gnomAD-4.0.0 | 1.92498E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.6186E-06 | 0 | 0 |
| D/H | rs2054587701 |
None | 1.0 | D | 0.591 | 0.461 | 0.343334270461 | gnomAD-4.0.0 | 1.61822E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.08318E-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 | 0.5964 | likely_pathogenic | 0.5143 | ambiguous | -0.321 | Destabilizing | 1.0 | D | 0.623 | neutral | N | 0.49581816 | None | None | N |
| D/C | 0.8907 | likely_pathogenic | 0.8571 | pathogenic | -0.23 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| D/E | 0.4001 | ambiguous | 0.3608 | ambiguous | -0.288 | Destabilizing | 1.0 | D | 0.402 | neutral | N | 0.494431293 | None | None | N |
| D/F | 0.8952 | likely_pathogenic | 0.8734 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| D/G | 0.3347 | likely_benign | 0.2719 | benign | -0.518 | Destabilizing | 1.0 | D | 0.547 | neutral | N | 0.411812697 | None | None | N |
| D/H | 0.7124 | likely_pathogenic | 0.6598 | pathogenic | 0.027 | Stabilizing | 1.0 | D | 0.591 | neutral | D | 0.523639479 | None | None | N |
| D/I | 0.8287 | likely_pathogenic | 0.7885 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| D/K | 0.8476 | likely_pathogenic | 0.8102 | pathogenic | -0.068 | Destabilizing | 1.0 | D | 0.585 | neutral | None | None | None | None | N |
| D/L | 0.7821 | likely_pathogenic | 0.7415 | pathogenic | 0.153 | Stabilizing | 1.0 | D | 0.687 | prob.neutral | None | None | None | None | N |
| D/M | 0.9072 | likely_pathogenic | 0.8811 | pathogenic | 0.156 | Stabilizing | 1.0 | D | 0.701 | prob.neutral | None | None | None | None | N |
| D/N | 0.223 | likely_benign | 0.1907 | benign | -0.221 | Destabilizing | 1.0 | D | 0.537 | neutral | N | 0.472322438 | None | None | N |
| D/P | 0.9367 | likely_pathogenic | 0.9177 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.59 | neutral | None | None | None | None | N |
| D/Q | 0.7222 | likely_pathogenic | 0.6873 | pathogenic | -0.185 | Destabilizing | 1.0 | D | 0.582 | neutral | None | None | None | None | N |
| D/R | 0.8302 | likely_pathogenic | 0.8134 | pathogenic | 0.23 | Stabilizing | 1.0 | D | 0.649 | neutral | None | None | None | None | N |
| D/S | 0.3697 | ambiguous | 0.3096 | benign | -0.391 | Destabilizing | 1.0 | D | 0.55 | neutral | None | None | None | None | N |
| D/T | 0.5567 | ambiguous | 0.4865 | ambiguous | -0.246 | Destabilizing | 1.0 | D | 0.591 | neutral | None | None | None | None | N |
| D/V | 0.7144 | likely_pathogenic | 0.6537 | pathogenic | 0.017 | Stabilizing | 1.0 | D | 0.689 | prob.neutral | N | 0.504707002 | None | None | N |
| D/W | 0.9633 | likely_pathogenic | 0.9574 | pathogenic | -0.106 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | N |
| D/Y | 0.638 | likely_pathogenic | 0.5964 | pathogenic | -0.009 | Destabilizing | 1.0 | D | 0.663 | neutral | N | 0.480513499 | 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.