Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 18050 | 54373;54374;54375 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| N2AB | 16409 | 49450;49451;49452 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| N2A | 15482 | 46669;46670;46671 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| N2B | 8985 | 27178;27179;27180 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| Novex-1 | 9110 | 27553;27554;27555 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| Novex-2 | 9177 | 27754;27755;27756 | chr2:178605029;178605028;178605027 | chr2:179469756;179469755;179469754 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/C | rs55734111  |
-0.05 | 1.0 | N | 0.439 | 0.401 | None | gnomAD-2.1.1 | 5.46575E-04 | None | None | None | None | I | None | 0 | 0 | None | 0 | 7.58984E-03 | None | 3.34E-05 | None | 0 | 0 | 4.27594E-04 |
| R/C | rs55734111 |
-0.05 | 1.0 | N | 0.439 | 0.401 | None | gnomAD-3.1.2 | 2.30272E-04 | None | None | None | None | I | None | 0 | 1.31182E-04 | 0 | 0 | 6.04053E-03 | None | 0 | 0 | 1.47E-05 | 0 | 4.78927E-04 |
| R/C | rs55734111 |
-0.05 | 1.0 | N | 0.439 | 0.401 | None | 1000 genomes | 1.39776E-03 | None | None | None | None | I | None | 0 | 0 | None | None | 6.9E-03 | 0 | None | None | None | 0 | None |
| R/C | rs55734111 |
-0.05 | 1.0 | N | 0.439 | 0.401 | None | gnomAD-4.0.0 | 1.64289E-04 | None | None | None | None | I | None | 1.3388E-05 | 3.35706E-05 | None | 0 | 4.4525E-03 | None | 0 | 3.32336E-04 | 1.3611E-05 | 2.21327E-05 | 6.75393E-04 |
| R/G | rs55734111 |
None | 0.961 | N | 0.473 | 0.32 | 0.574160883478 | gnomAD-4.0.0 | 2.7495E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.61149E-06 | 0 | 0 |
| R/H | rs774572776 |
None | 0.999 | N | 0.415 | 0.318 | 0.33340067248 | gnomAD-4.0.0 | 9.6299E-06 | None | None | None | None | I | None | 3.01768E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 1.08391E-05 | 1.17275E-05 | 0 |
| R/L | rs774572776 |
0.508 | 0.992 | N | 0.543 | 0.384 | 0.599314493506 | gnomAD-2.1.1 | 4.1E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 9.05E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.7141 | likely_pathogenic | 0.6982 | pathogenic | 0.121 | Stabilizing | 0.927 | D | 0.455 | neutral | None | None | None | None | I |
| R/C | 0.4304 | ambiguous | 0.4442 | ambiguous | -0.156 | Destabilizing | 1.0 | D | 0.439 | neutral | N | 0.497330817 | None | None | I |
| R/D | 0.8727 | likely_pathogenic | 0.8541 | pathogenic | -0.251 | Destabilizing | 0.939 | D | 0.553 | neutral | None | None | None | None | I |
| R/E | 0.7175 | likely_pathogenic | 0.6848 | pathogenic | -0.197 | Destabilizing | 0.927 | D | 0.429 | neutral | None | None | None | None | I |
| R/F | 0.8364 | likely_pathogenic | 0.8061 | pathogenic | -0.17 | Destabilizing | 0.999 | D | 0.441 | neutral | None | None | None | None | I |
| R/G | 0.6435 | likely_pathogenic | 0.6035 | pathogenic | -0.04 | Destabilizing | 0.961 | D | 0.473 | neutral | N | 0.457772352 | None | None | I |
| R/H | 0.2319 | likely_benign | 0.2046 | benign | -0.607 | Destabilizing | 0.999 | D | 0.415 | neutral | N | 0.515569861 | None | None | I |
| R/I | 0.5031 | ambiguous | 0.497 | ambiguous | 0.502 | Stabilizing | 0.999 | D | 0.475 | neutral | None | None | None | None | I |
| R/K | 0.2767 | likely_benign | 0.2611 | benign | -0.059 | Destabilizing | 0.148 | N | 0.199 | neutral | None | None | None | None | I |
| R/L | 0.5186 | ambiguous | 0.4999 | ambiguous | 0.502 | Stabilizing | 0.992 | D | 0.543 | neutral | N | 0.474107241 | None | None | I |
| R/M | 0.6568 | likely_pathogenic | 0.6331 | pathogenic | -0.005 | Destabilizing | 0.999 | D | 0.451 | neutral | None | None | None | None | I |
| R/N | 0.7672 | likely_pathogenic | 0.7596 | pathogenic | 0.028 | Stabilizing | 0.148 | N | 0.157 | neutral | None | None | None | None | I |
| R/P | 0.7446 | likely_pathogenic | 0.686 | pathogenic | 0.395 | Stabilizing | 0.999 | D | 0.517 | neutral | N | 0.448075433 | None | None | I |
| R/Q | 0.2434 | likely_benign | 0.2258 | benign | 0.004 | Stabilizing | 0.969 | D | 0.491 | neutral | None | None | None | None | I |
| R/S | 0.7683 | likely_pathogenic | 0.7524 | pathogenic | -0.149 | Destabilizing | 0.961 | D | 0.457 | neutral | N | 0.431505683 | None | None | I |
| R/T | 0.5848 | likely_pathogenic | 0.5771 | pathogenic | 0.022 | Stabilizing | 0.969 | D | 0.524 | neutral | None | None | None | None | I |
| R/V | 0.5997 | likely_pathogenic | 0.6033 | pathogenic | 0.395 | Stabilizing | 0.995 | D | 0.486 | neutral | None | None | None | None | I |
| R/W | 0.5487 | ambiguous | 0.492 | ambiguous | -0.349 | Destabilizing | 1.0 | D | 0.521 | neutral | None | None | None | None | I |
| R/Y | 0.708 | likely_pathogenic | 0.6553 | pathogenic | 0.073 | Stabilizing | 0.999 | D | 0.482 | 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.