Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24828 | 74707;74708;74709 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| N2AB | 23187 | 69784;69785;69786 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| N2A | 22260 | 67003;67004;67005 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| N2B | 15763 | 47512;47513;47514 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| Novex-1 | 15888 | 47887;47888;47889 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| Novex-2 | 15955 | 48088;48089;48090 | chr2:178571650;178571649;178571648 | chr2:179436377;179436376;179436375 |
| 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/F | rs375181431  |
-1.633 | 0.001 | N | 0.401 | 0.236 | 0.435590266561 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| L/V | rs375181431 |
-1.519 | 0.009 | N | 0.495 | 0.07 | None | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.96E-06 | 0 |
| L/V | rs375181431 |
-1.519 | 0.009 | N | 0.495 | 0.07 | None | 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 |
| L/V | rs375181431 |
-1.519 | 0.009 | N | 0.495 | 0.07 | None | gnomAD-4.0.0 | 2.5636E-06 | None | None | None | None | N | None | 3.38387E-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 | 0.8469 | likely_pathogenic | 0.8436 | pathogenic | -2.718 | Highly Destabilizing | 0.149 | N | 0.729 | prob.delet. | None | None | None | None | N |
| L/C | 0.6972 | likely_pathogenic | 0.6923 | pathogenic | -2.251 | Highly Destabilizing | 0.935 | D | 0.787 | deleterious | None | None | None | None | N |
| L/D | 0.9978 | likely_pathogenic | 0.9979 | pathogenic | -3.342 | Highly Destabilizing | 0.555 | D | 0.879 | deleterious | None | None | None | None | N |
| L/E | 0.9901 | likely_pathogenic | 0.9906 | pathogenic | -3.035 | Highly Destabilizing | 0.555 | D | 0.87 | deleterious | None | None | None | None | N |
| L/F | 0.1605 | likely_benign | 0.1525 | benign | -1.648 | Destabilizing | 0.001 | N | 0.401 | neutral | N | 0.514139385 | None | None | N |
| L/G | 0.9774 | likely_pathogenic | 0.9788 | pathogenic | -3.345 | Highly Destabilizing | 0.555 | D | 0.845 | deleterious | None | None | None | None | N |
| L/H | 0.9531 | likely_pathogenic | 0.9524 | pathogenic | -3.023 | Highly Destabilizing | 0.78 | D | 0.883 | deleterious | D | 0.558857045 | None | None | N |
| L/I | 0.0714 | likely_benign | 0.0643 | benign | -0.856 | Destabilizing | None | N | 0.239 | neutral | N | 0.506155371 | None | None | N |
| L/K | 0.9823 | likely_pathogenic | 0.983 | pathogenic | -2.114 | Highly Destabilizing | 0.555 | D | 0.826 | deleterious | None | None | None | None | N |
| L/M | 0.1475 | likely_benign | 0.1496 | benign | -1.077 | Destabilizing | 0.035 | N | 0.418 | neutral | None | None | None | None | N |
| L/N | 0.9852 | likely_pathogenic | 0.9857 | pathogenic | -2.738 | Highly Destabilizing | 0.791 | D | 0.882 | deleterious | None | None | None | None | N |
| L/P | 0.9858 | likely_pathogenic | 0.9845 | pathogenic | -1.464 | Destabilizing | 0.741 | D | 0.885 | deleterious | D | 0.558857045 | None | None | N |
| L/Q | 0.9574 | likely_pathogenic | 0.959 | pathogenic | -2.432 | Highly Destabilizing | 0.555 | D | 0.861 | deleterious | None | None | None | None | N |
| L/R | 0.9674 | likely_pathogenic | 0.9659 | pathogenic | -2.072 | Highly Destabilizing | 0.484 | N | 0.856 | deleterious | D | 0.558857045 | None | None | N |
| L/S | 0.9683 | likely_pathogenic | 0.9693 | pathogenic | -3.408 | Highly Destabilizing | 0.555 | D | 0.813 | deleterious | None | None | None | None | N |
| L/T | 0.9074 | likely_pathogenic | 0.9117 | pathogenic | -2.928 | Highly Destabilizing | 0.149 | N | 0.764 | deleterious | None | None | None | None | N |
| L/V | 0.1017 | likely_benign | 0.1009 | benign | -1.464 | Destabilizing | 0.009 | N | 0.495 | neutral | N | 0.511193044 | None | None | N |
| L/W | 0.7797 | likely_pathogenic | 0.7621 | pathogenic | -2.102 | Highly Destabilizing | 0.824 | D | 0.86 | deleterious | None | None | None | None | N |
| L/Y | 0.7981 | likely_pathogenic | 0.7825 | pathogenic | -1.83 | Destabilizing | 0.235 | N | 0.775 | deleterious | None | None | 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.