Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20286 | 61081;61082;61083 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| N2AB | 18645 | 56158;56159;56160 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| N2A | 17718 | 53377;53378;53379 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| N2B | 11221 | 33886;33887;33888 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| Novex-1 | 11346 | 34261;34262;34263 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| Novex-2 | 11413 | 34462;34463;34464 | chr2:178590869;178590868;178590867 | chr2:179455596;179455595;179455594 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/S | rs553761018  |
-0.14 | 0.016 | N | 0.156 | 0.095 | 0.141422826196 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| N/S | rs553761018 |
-0.14 | 0.016 | N | 0.156 | 0.095 | 0.141422826196 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| N/S | rs553761018 |
-0.14 | 0.016 | N | 0.156 | 0.095 | 0.141422826196 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 0 | None | None | 0 | 1E-03 | None | None | None | 0 | None |
| N/S | rs553761018 |
-0.14 | 0.016 | N | 0.156 | 0.095 | 0.141422826196 | gnomAD-4.0.0 | 2.57472E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 4.8223E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.3066 | likely_benign | 0.4746 | ambiguous | -0.628 | Destabilizing | 0.25 | N | 0.375 | neutral | None | None | None | None | N |
| N/C | 0.3907 | ambiguous | 0.5303 | ambiguous | 0.236 | Stabilizing | 0.992 | D | 0.457 | neutral | None | None | None | None | N |
| N/D | 0.155 | likely_benign | 0.2097 | benign | -0.447 | Destabilizing | 0.002 | N | 0.079 | neutral | N | 0.40663895 | None | None | N |
| N/E | 0.4166 | ambiguous | 0.5663 | pathogenic | -0.469 | Destabilizing | 0.25 | N | 0.379 | neutral | None | None | None | None | N |
| N/F | 0.5832 | likely_pathogenic | 0.6974 | pathogenic | -0.933 | Destabilizing | 0.92 | D | 0.441 | neutral | None | None | None | None | N |
| N/G | 0.3495 | ambiguous | 0.4811 | ambiguous | -0.821 | Destabilizing | 0.25 | N | 0.375 | neutral | None | None | None | None | N |
| N/H | 0.1608 | likely_benign | 0.2211 | benign | -0.87 | Destabilizing | 0.896 | D | 0.443 | neutral | N | 0.478309834 | None | None | N |
| N/I | 0.3651 | ambiguous | 0.5283 | ambiguous | -0.191 | Destabilizing | 0.896 | D | 0.443 | neutral | N | 0.476790516 | None | None | N |
| N/K | 0.4094 | ambiguous | 0.5718 | pathogenic | -0.019 | Destabilizing | 0.379 | N | 0.377 | neutral | N | 0.504725645 | None | None | N |
| N/L | 0.3594 | ambiguous | 0.4841 | ambiguous | -0.191 | Destabilizing | 0.85 | D | 0.406 | neutral | None | None | None | None | N |
| N/M | 0.3329 | likely_benign | 0.4505 | ambiguous | 0.474 | Stabilizing | 0.992 | D | 0.411 | neutral | None | None | None | None | N |
| N/P | 0.9358 | likely_pathogenic | 0.9727 | pathogenic | -0.311 | Destabilizing | 0.92 | D | 0.423 | neutral | None | None | None | None | N |
| N/Q | 0.4238 | ambiguous | 0.5666 | pathogenic | -0.691 | Destabilizing | 0.85 | D | 0.417 | neutral | None | None | None | None | N |
| N/R | 0.5242 | ambiguous | 0.668 | pathogenic | 0.134 | Stabilizing | 0.85 | D | 0.415 | neutral | None | None | None | None | N |
| N/S | 0.1062 | likely_benign | 0.158 | benign | -0.355 | Destabilizing | 0.016 | N | 0.156 | neutral | N | 0.432265327 | None | None | N |
| N/T | 0.1194 | likely_benign | 0.1787 | benign | -0.233 | Destabilizing | 0.379 | N | 0.347 | neutral | N | 0.454464609 | None | None | N |
| N/V | 0.3618 | ambiguous | 0.5222 | ambiguous | -0.311 | Destabilizing | 0.85 | D | 0.417 | neutral | None | None | None | None | N |
| N/W | 0.8044 | likely_pathogenic | 0.8844 | pathogenic | -0.799 | Destabilizing | 0.992 | D | 0.589 | neutral | None | None | None | None | N |
| N/Y | 0.1883 | likely_benign | 0.2501 | benign | -0.561 | Destabilizing | 0.963 | D | 0.425 | neutral | N | 0.52167661 | 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.