Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 3261 | 10006;10007;10008 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| N2AB | 3261 | 10006;10007;10008 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| N2A | 3261 | 10006;10007;10008 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| N2B | 3215 | 9868;9869;9870 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| Novex-1 | 3215 | 9868;9869;9870 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| Novex-2 | 3215 | 9868;9869;9870 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
| Novex-3 | 3261 | 10006;10007;10008 | chr2:178764734;178764733;178764732 | chr2:179629461;179629460;179629459 |
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/L | rs2291311  |
None | 0.679 | N | 0.487 | 0.203 | 0.426436156839 | gnomAD-4.0.0 | 4.10457E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39583E-06 | 0 | 0 |
| V/M | rs2291311 |
-0.845 | 0.988 | N | 0.588 | 0.235 | None | gnomAD-2.1.1 | 8.44463E-01 | None | None | None | None | N | None | 8.29898E-01 | 5.72776E-01 | None | 9.13783E-01 | 7.69246E-01 | None | 7.88893E-01 | None | 8.9176E-01 | 9.30365E-01 | 8.75902E-01 |
| V/M | rs2291311 |
-0.845 | 0.988 | N | 0.588 | 0.235 | None | gnomAD-3.1.2 | 8.69609E-01 | None | None | None | None | N | None | 8.30739E-01 | 7.18902E-01 | 9.51754E-01 | 9.18491E-01 | 7.9059E-01 | None | 8.91522E-01 | 9.49367E-01 | 9.30493E-01 | 7.91373E-01 | 8.93881E-01 |
| V/M | rs2291311 |
-0.845 | 0.988 | N | 0.588 | 0.235 | None | 1000 genomes | 8.04912E-01 | None | None | None | None | N | None | 8.253E-01 | 6.671E-01 | None | None | 7.847E-01 | 9.145E-01 | None | None | None | 7.832E-01 | None |
| V/M | rs2291311 |
-0.845 | 0.988 | N | 0.588 | 0.235 | None | gnomAD-4.0.0 | 9.0011E-01 | None | None | None | None | N | None | 8.29923E-01 | 6.19412E-01 | None | 9.17016E-01 | 7.91147E-01 | None | 8.89401E-01 | 9.29377E-01 | 9.31221E-01 | 7.95893E-01 | 8.95827E-01 |
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 | 0.2073 | likely_benign | 0.3006 | benign | -1.794 | Destabilizing | 0.625 | D | 0.497 | neutral | N | 0.498429074 | None | None | N |
| V/C | 0.8106 | likely_pathogenic | 0.8765 | pathogenic | -1.296 | Destabilizing | 0.998 | D | 0.551 | neutral | None | None | None | None | N |
| V/D | 0.5543 | ambiguous | 0.7292 | pathogenic | -1.917 | Destabilizing | 0.728 | D | 0.617 | neutral | None | None | None | None | N |
| V/E | 0.2894 | likely_benign | 0.3715 | ambiguous | -1.853 | Destabilizing | 0.022 | N | 0.369 | neutral | N | 0.43608088 | None | None | N |
| V/F | 0.195 | likely_benign | 0.2915 | benign | -1.221 | Destabilizing | 0.949 | D | 0.585 | neutral | None | None | None | None | N |
| V/G | 0.3554 | ambiguous | 0.504 | ambiguous | -2.171 | Highly Destabilizing | 0.891 | D | 0.611 | neutral | N | 0.500830961 | None | None | N |
| V/H | 0.5967 | likely_pathogenic | 0.7121 | pathogenic | -1.672 | Destabilizing | 0.974 | D | 0.599 | neutral | None | None | None | None | N |
| V/I | 0.0728 | likely_benign | 0.0814 | benign | -0.818 | Destabilizing | 0.016 | N | 0.268 | neutral | None | None | None | None | N |
| V/K | 0.2861 | likely_benign | 0.3848 | ambiguous | -1.487 | Destabilizing | 0.525 | D | 0.562 | neutral | None | None | None | None | N |
| V/L | 0.1706 | likely_benign | 0.2335 | benign | -0.818 | Destabilizing | 0.679 | D | 0.487 | neutral | N | 0.500227614 | None | None | N |
| V/M | 0.1047 | likely_benign | 0.114 | benign | -0.728 | Destabilizing | 0.988 | D | 0.588 | neutral | N | 0.512031569 | None | None | N |
| V/N | 0.3378 | likely_benign | 0.5006 | ambiguous | -1.426 | Destabilizing | 0.915 | D | 0.646 | neutral | None | None | None | None | N |
| V/P | 0.9374 | likely_pathogenic | 0.9795 | pathogenic | -1.112 | Destabilizing | 0.991 | D | 0.601 | neutral | None | None | None | None | N |
| V/Q | 0.2951 | likely_benign | 0.3454 | ambiguous | -1.536 | Destabilizing | 0.172 | N | 0.523 | neutral | None | None | None | None | N |
| V/R | 0.268 | likely_benign | 0.3478 | ambiguous | -1.002 | Destabilizing | 0.067 | N | 0.567 | neutral | None | None | None | None | N |
| V/S | 0.2678 | likely_benign | 0.3767 | ambiguous | -1.992 | Destabilizing | 0.842 | D | 0.571 | neutral | None | None | None | None | N |
| V/T | 0.1997 | likely_benign | 0.2594 | benign | -1.82 | Destabilizing | 0.842 | D | 0.521 | neutral | None | None | None | None | N |
| V/W | 0.8522 | likely_pathogenic | 0.9143 | pathogenic | -1.497 | Destabilizing | 0.998 | D | 0.629 | neutral | None | None | None | None | N |
| V/Y | 0.6191 | likely_pathogenic | 0.7428 | pathogenic | -1.196 | Destabilizing | 0.991 | D | 0.587 | neutral | 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.