Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19195 | 57808;57809;57810 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| N2AB | 17554 | 52885;52886;52887 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| N2A | 16627 | 50104;50105;50106 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| N2B | 10130 | 30613;30614;30615 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| Novex-1 | 10255 | 30988;30989;30990 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| Novex-2 | 10322 | 31189;31190;31191 | chr2:178595771;178595770;178595769 | chr2:179460498;179460497;179460496 |
| 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/H | rs757544346  |
-0.903 | 1.0 | N | 0.665 | 0.435 | 0.318540980066 | gnomAD-2.1.1 | 4.18E-06 | None | None | None | None | N | None | 6.75E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| N/H | rs757544346 |
-0.903 | 1.0 | N | 0.665 | 0.435 | 0.318540980066 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/H | rs757544346 |
-0.903 | 1.0 | N | 0.665 | 0.435 | 0.318540980066 | gnomAD-4.0.0 | 2.58081E-06 | None | None | None | None | N | None | 3.38765E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| N/S | rs754292868 |
-0.357 | 0.999 | N | 0.484 | 0.352 | 0.267755039894 | gnomAD-2.1.1 | 8.35E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.82E-05 | None | 0 | None | 0 | 9.23E-06 | 0 |
| N/S | rs754292868 |
-0.357 | 0.999 | N | 0.484 | 0.352 | 0.267755039894 | gnomAD-4.0.0 | 4.1206E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.54414E-05 | None | 0 | 0 | 3.60554E-06 | 1.17908E-05 | 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 | 0.3123 | likely_benign | 0.3192 | benign | -0.304 | Destabilizing | 1.0 | D | 0.699 | prob.neutral | None | None | None | None | N |
| N/C | 0.3359 | likely_benign | 0.3358 | benign | 0.353 | Stabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| N/D | 0.1855 | likely_benign | 0.201 | benign | 0.122 | Stabilizing | 0.999 | D | 0.523 | neutral | N | 0.446888062 | None | None | N |
| N/E | 0.5005 | ambiguous | 0.528 | ambiguous | 0.092 | Stabilizing | 0.999 | D | 0.653 | neutral | None | None | None | None | N |
| N/F | 0.5776 | likely_pathogenic | 0.5884 | pathogenic | -0.63 | Destabilizing | 1.0 | D | 0.77 | deleterious | None | None | None | None | N |
| N/G | 0.3047 | likely_benign | 0.311 | benign | -0.485 | Destabilizing | 0.999 | D | 0.499 | neutral | None | None | None | None | N |
| N/H | 0.1261 | likely_benign | 0.135 | benign | -0.5 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.470776581 | None | None | N |
| N/I | 0.3438 | ambiguous | 0.3719 | ambiguous | 0.088 | Stabilizing | 1.0 | D | 0.803 | deleterious | N | 0.474246075 | None | None | N |
| N/K | 0.5474 | ambiguous | 0.5782 | pathogenic | -0.004 | Destabilizing | 1.0 | D | 0.665 | neutral | N | 0.518924306 | None | None | N |
| N/L | 0.3112 | likely_benign | 0.3325 | benign | 0.088 | Stabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/M | 0.4535 | ambiguous | 0.4613 | ambiguous | 0.312 | Stabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | N |
| N/P | 0.7357 | likely_pathogenic | 0.7853 | pathogenic | -0.016 | Destabilizing | 1.0 | D | 0.789 | deleterious | None | None | None | None | N |
| N/Q | 0.4161 | ambiguous | 0.4287 | ambiguous | -0.316 | Destabilizing | 1.0 | D | 0.684 | prob.neutral | None | None | None | None | N |
| N/R | 0.5335 | ambiguous | 0.5615 | ambiguous | 0.033 | Stabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| N/S | 0.1 | likely_benign | 0.1006 | benign | -0.13 | Destabilizing | 0.999 | D | 0.484 | neutral | N | 0.481173994 | None | None | N |
| N/T | 0.1921 | likely_benign | 0.2027 | benign | -0.023 | Destabilizing | 0.999 | D | 0.639 | neutral | N | 0.513363771 | None | None | N |
| N/V | 0.3447 | ambiguous | 0.3655 | ambiguous | -0.016 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| N/W | 0.8235 | likely_pathogenic | 0.8414 | pathogenic | -0.646 | Destabilizing | 1.0 | D | 0.735 | prob.delet. | None | None | None | None | N |
| N/Y | 0.222 | likely_benign | 0.2367 | benign | -0.387 | Destabilizing | 1.0 | D | 0.763 | deleterious | N | 0.470776581 | 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.