Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 4730 | 14413;14414;14415 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| N2AB | 4413 | 13462;13463;13464 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| N2A | 3486 | 10681;10682;10683 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| N2B | 4367 | 13324;13325;13326 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| Novex-1 | 4492 | 13699;13700;13701 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| Novex-2 | 4559 | 13900;13901;13902 | chr2:178738265;178738264;178738263 | chr2:179602992;179602991;179602990 |
| 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/L | None | None | 0.82 | N | 0.516 | 0.356 | 0.468586609112 | gnomAD-4.0.0 | 6.84332E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9953E-07 | 0 | 0 |
| R/Q | rs202017278  |
0.176 | 0.91 | N | 0.527 | 0.263 | None | gnomAD-2.1.1 | 2.86E-05 | None | None | None | None | I | None | 1.24069E-04 | 0 | None | 0 | 0 | None | 6.54E-05 | None | 0 | 2.35E-05 | 0 |
| R/Q | rs202017278 |
0.176 | 0.91 | N | 0.527 | 0.263 | None | gnomAD-3.1.2 | 3.94E-05 | None | None | None | None | I | None | 1.2068E-04 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/Q | rs202017278 |
0.176 | 0.91 | N | 0.527 | 0.263 | None | gnomAD-4.0.0 | 8.11942E-05 | None | None | None | None | I | None | 9.34554E-05 | 0 | None | 0 | 0 | None | 0 | 1.64474E-04 | 9.66334E-05 | 5.49185E-05 | 6.40656E-05 |
| R/W | rs749719834 |
-0.441 | 0.999 | N | 0.435 | 0.408 | 0.539478914628 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 1.29282E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| R/W | rs749719834 |
-0.441 | 0.999 | N | 0.435 | 0.408 | 0.539478914628 | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| R/W | rs749719834 |
-0.441 | 0.999 | N | 0.435 | 0.408 | 0.539478914628 | gnomAD-4.0.0 | 8.67716E-06 | None | None | None | None | I | None | 4.00491E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 9.32428E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.4897 | ambiguous | 0.6037 | pathogenic | -0.206 | Destabilizing | 0.495 | N | 0.371 | neutral | None | None | None | None | I |
| R/C | 0.2155 | likely_benign | 0.279 | benign | -0.339 | Destabilizing | 0.995 | D | 0.425 | neutral | None | None | None | None | I |
| R/D | 0.6968 | likely_pathogenic | 0.7903 | pathogenic | 0.004 | Stabilizing | 0.543 | D | 0.513 | neutral | None | None | None | None | I |
| R/E | 0.4322 | ambiguous | 0.539 | ambiguous | 0.073 | Stabilizing | 0.329 | N | 0.435 | neutral | None | None | None | None | I |
| R/F | 0.6233 | likely_pathogenic | 0.7115 | pathogenic | -0.392 | Destabilizing | 0.981 | D | 0.456 | neutral | None | None | None | None | I |
| R/G | 0.3596 | ambiguous | 0.4875 | ambiguous | -0.414 | Destabilizing | 0.006 | N | 0.302 | neutral | N | 0.398330804 | None | None | I |
| R/H | 0.1058 | likely_benign | 0.1304 | benign | -0.794 | Destabilizing | 0.944 | D | 0.521 | neutral | None | None | None | None | I |
| R/I | 0.2874 | likely_benign | 0.3557 | ambiguous | 0.31 | Stabilizing | 0.893 | D | 0.515 | neutral | None | None | None | None | I |
| R/K | 0.1251 | likely_benign | 0.1439 | benign | -0.233 | Destabilizing | 0.003 | N | 0.185 | neutral | None | None | None | None | I |
| R/L | 0.3129 | likely_benign | 0.388 | ambiguous | 0.31 | Stabilizing | 0.82 | D | 0.516 | neutral | N | 0.443142171 | None | None | I |
| R/M | 0.3475 | ambiguous | 0.4393 | ambiguous | -0.062 | Destabilizing | 0.981 | D | 0.495 | neutral | None | None | None | None | I |
| R/N | 0.5683 | likely_pathogenic | 0.6651 | pathogenic | 0.073 | Stabilizing | 0.031 | N | 0.204 | neutral | None | None | None | None | I |
| R/P | 0.8465 | likely_pathogenic | 0.9057 | pathogenic | 0.159 | Stabilizing | 0.902 | D | 0.579 | neutral | N | 0.443607298 | None | None | I |
| R/Q | 0.1234 | likely_benign | 0.1547 | benign | -0.078 | Destabilizing | 0.91 | D | 0.527 | neutral | N | 0.382449142 | None | None | I |
| R/S | 0.4938 | ambiguous | 0.6163 | pathogenic | -0.419 | Destabilizing | 0.329 | N | 0.439 | neutral | None | None | None | None | I |
| R/T | 0.2413 | likely_benign | 0.327 | benign | -0.208 | Destabilizing | 0.013 | N | 0.262 | neutral | None | None | None | None | I |
| R/V | 0.3841 | ambiguous | 0.4615 | ambiguous | 0.159 | Stabilizing | 0.704 | D | 0.554 | neutral | None | None | None | None | I |
| R/W | 0.22 | likely_benign | 0.2704 | benign | -0.349 | Destabilizing | 0.999 | D | 0.435 | neutral | N | 0.443844982 | None | None | I |
| R/Y | 0.4205 | ambiguous | 0.5074 | ambiguous | 0.04 | Stabilizing | 0.981 | D | 0.478 | 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.