Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 28488 | 85687;85688;85689 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| N2AB | 26847 | 80764;80765;80766 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| N2A | 25920 | 77983;77984;77985 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| N2B | 19423 | 58492;58493;58494 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| Novex-1 | 19548 | 58867;58868;58869 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| Novex-2 | 19615 | 59068;59069;59070 | chr2:178560670;178560669;178560668 | chr2:179425397;179425396;179425395 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/I | rs377264123  |
-0.773 | 0.428 | N | 0.317 | 0.086 | None | gnomAD-2.1.1 | 6.8E-05 | None | None | None | None | N | None | 2.06868E-04 | 2.83E-05 | None | 0 | 1.5448E-04 | None | 0 | None | 0 | 7.84E-05 | 0 |
| V/I | rs377264123 |
-0.773 | 0.428 | N | 0.317 | 0.086 | None | gnomAD-3.1.2 | 6.57E-05 | None | None | None | None | N | None | 1.4476E-04 | 1.3113E-04 | 0 | 0 | 0 | None | 0 | 0 | 2.94E-05 | 0 | 0 |
| V/I | rs377264123 |
-0.773 | 0.428 | N | 0.317 | 0.086 | None | gnomAD-4.0.0 | 3.40879E-05 | None | None | None | None | N | None | 1.20138E-04 | 5.003E-05 | None | 0 | 6.69493E-05 | None | 0 | 0 | 3.13622E-05 | 1.09806E-05 | 3.20256E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.6157 | likely_pathogenic | 0.5903 | pathogenic | -2.529 | Highly Destabilizing | 0.977 | D | 0.632 | neutral | D | 0.557771089 | None | None | N |
| V/C | 0.9408 | likely_pathogenic | 0.9355 | pathogenic | -2.14 | Highly Destabilizing | 1.0 | D | 0.813 | deleterious | None | None | None | None | N |
| V/D | 0.9958 | likely_pathogenic | 0.9948 | pathogenic | -3.43 | Highly Destabilizing | 0.999 | D | 0.884 | deleterious | None | None | None | None | N |
| V/E | 0.9851 | likely_pathogenic | 0.9825 | pathogenic | -3.136 | Highly Destabilizing | 0.999 | D | 0.871 | deleterious | D | 0.558531558 | None | None | N |
| V/F | 0.7783 | likely_pathogenic | 0.7681 | pathogenic | -1.432 | Destabilizing | 0.995 | D | 0.831 | deleterious | None | None | None | None | N |
| V/G | 0.8823 | likely_pathogenic | 0.8675 | pathogenic | -3.137 | Highly Destabilizing | 0.999 | D | 0.882 | deleterious | D | 0.558531558 | None | None | N |
| V/H | 0.9942 | likely_pathogenic | 0.9932 | pathogenic | -2.921 | Highly Destabilizing | 1.0 | D | 0.877 | deleterious | None | None | None | None | N |
| V/I | 0.0907 | likely_benign | 0.0882 | benign | -0.774 | Destabilizing | 0.428 | N | 0.317 | neutral | N | 0.472578728 | None | None | N |
| V/K | 0.9798 | likely_pathogenic | 0.9768 | pathogenic | -2.166 | Highly Destabilizing | 0.998 | D | 0.873 | deleterious | None | None | None | None | N |
| V/L | 0.3831 | ambiguous | 0.3516 | ambiguous | -0.774 | Destabilizing | 0.957 | D | 0.581 | neutral | N | 0.498826753 | None | None | N |
| V/M | 0.5237 | ambiguous | 0.4757 | ambiguous | -0.987 | Destabilizing | 0.995 | D | 0.747 | deleterious | None | None | None | None | N |
| V/N | 0.9888 | likely_pathogenic | 0.9865 | pathogenic | -2.74 | Highly Destabilizing | 0.999 | D | 0.893 | deleterious | None | None | None | None | N |
| V/P | 0.9837 | likely_pathogenic | 0.9796 | pathogenic | -1.338 | Destabilizing | 0.999 | D | 0.88 | deleterious | None | None | None | None | N |
| V/Q | 0.9775 | likely_pathogenic | 0.9745 | pathogenic | -2.447 | Highly Destabilizing | 0.999 | D | 0.899 | deleterious | None | None | None | None | N |
| V/R | 0.9625 | likely_pathogenic | 0.9578 | pathogenic | -2.097 | Highly Destabilizing | 0.999 | D | 0.898 | deleterious | None | None | None | None | N |
| V/S | 0.9302 | likely_pathogenic | 0.9203 | pathogenic | -3.334 | Highly Destabilizing | 0.998 | D | 0.878 | deleterious | None | None | None | None | N |
| V/T | 0.7348 | likely_pathogenic | 0.7085 | pathogenic | -2.883 | Highly Destabilizing | 0.983 | D | 0.699 | prob.neutral | None | None | None | None | N |
| V/W | 0.9922 | likely_pathogenic | 0.9911 | pathogenic | -2.023 | Highly Destabilizing | 1.0 | D | 0.857 | deleterious | None | None | None | None | N |
| V/Y | 0.9785 | likely_pathogenic | 0.9756 | pathogenic | -1.701 | Destabilizing | 0.999 | D | 0.831 | 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.