Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17502 | 52729;52730;52731 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| N2AB | 15861 | 47806;47807;47808 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| N2A | 14934 | 45025;45026;45027 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| N2B | 8437 | 25534;25535;25536 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| Novex-1 | 8562 | 25909;25910;25911 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| Novex-2 | 8629 | 26110;26111;26112 | chr2:178608379;178608378;178608377 | chr2:179473106;179473105;179473104 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/S | rs368013299  |
-0.495 | 0.81 | N | 0.404 | 0.312 | None | gnomAD-2.1.1 | 1.09E-05 | None | None | None | None | I | None | 8.35E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 7.93E-06 | 0 |
| L/S | rs368013299 |
-0.495 | 0.81 | N | 0.404 | 0.312 | None | gnomAD-3.1.2 | 1.97E-05 | None | None | None | None | I | None | 7.24E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/S | rs368013299 |
-0.495 | 0.81 | N | 0.404 | 0.312 | None | gnomAD-4.0.0 | 4.9642E-06 | None | None | None | None | I | None | 6.68021E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 2.54491E-06 | 0 | 0 |
| L/W | rs368013299 |
None | 0.99 | N | 0.615 | 0.539 | 0.826545055579 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| L/W | rs368013299 |
None | 0.99 | N | 0.615 | 0.539 | 0.826545055579 | gnomAD-4.0.0 | 6.57825E-06 | None | None | None | None | I | None | 2.41324E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| L/A | 0.1672 | likely_benign | 0.1687 | benign | -0.947 | Destabilizing | 0.447 | N | 0.397 | neutral | None | None | None | None | I |
| L/C | 0.4745 | ambiguous | 0.4722 | ambiguous | -0.695 | Destabilizing | 0.992 | D | 0.459 | neutral | None | None | None | None | I |
| L/D | 0.6347 | likely_pathogenic | 0.6467 | pathogenic | -0.387 | Destabilizing | 0.739 | D | 0.477 | neutral | None | None | None | None | I |
| L/E | 0.3046 | likely_benign | 0.3037 | benign | -0.455 | Destabilizing | 0.048 | N | 0.39 | neutral | None | None | None | None | I |
| L/F | 0.1658 | likely_benign | 0.1653 | benign | -0.757 | Destabilizing | 0.81 | D | 0.449 | neutral | N | 0.492399555 | None | None | I |
| L/G | 0.5024 | ambiguous | 0.5107 | ambiguous | -1.163 | Destabilizing | 0.92 | D | 0.453 | neutral | None | None | None | None | I |
| L/H | 0.2042 | likely_benign | 0.2016 | benign | -0.325 | Destabilizing | 0.992 | D | 0.487 | neutral | None | None | None | None | I |
| L/I | 0.0635 | likely_benign | 0.0668 | benign | -0.481 | Destabilizing | 0.005 | N | 0.209 | neutral | None | None | None | None | I |
| L/K | 0.2341 | likely_benign | 0.2243 | benign | -0.589 | Destabilizing | 0.85 | D | 0.41 | neutral | None | None | None | None | I |
| L/M | 0.1057 | likely_benign | 0.1054 | benign | -0.454 | Destabilizing | 0.099 | N | 0.213 | neutral | N | 0.521964611 | None | None | I |
| L/N | 0.2856 | likely_benign | 0.2977 | benign | -0.377 | Destabilizing | 0.92 | D | 0.497 | neutral | None | None | None | None | I |
| L/P | 0.8386 | likely_pathogenic | 0.8043 | pathogenic | -0.602 | Destabilizing | 0.972 | D | 0.494 | neutral | None | None | None | None | I |
| L/Q | 0.131 | likely_benign | 0.1275 | benign | -0.606 | Destabilizing | 0.85 | D | 0.481 | neutral | None | None | None | None | I |
| L/R | 0.185 | likely_benign | 0.1713 | benign | 0.034 | Stabilizing | 0.85 | D | 0.481 | neutral | None | None | None | None | I |
| L/S | 0.1746 | likely_benign | 0.1929 | benign | -0.889 | Destabilizing | 0.81 | D | 0.404 | neutral | N | 0.474536024 | None | None | I |
| L/T | 0.0946 | likely_benign | 0.0936 | benign | -0.845 | Destabilizing | 0.617 | D | 0.379 | neutral | None | None | None | None | I |
| L/V | 0.0763 | likely_benign | 0.077 | benign | -0.602 | Destabilizing | 0.004 | N | 0.096 | neutral | N | 0.515382568 | None | None | I |
| L/W | 0.3516 | ambiguous | 0.3391 | benign | -0.76 | Destabilizing | 0.99 | D | 0.615 | neutral | N | 0.511010789 | None | None | I |
| L/Y | 0.4033 | ambiguous | 0.4032 | ambiguous | -0.536 | Destabilizing | 0.92 | D | 0.453 | 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.