Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22416 | 67471;67472;67473 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| N2AB | 20775 | 62548;62549;62550 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| N2A | 19848 | 59767;59768;59769 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| N2B | 13351 | 40276;40277;40278 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| Novex-1 | 13476 | 40651;40652;40653 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| Novex-2 | 13543 | 40852;40853;40854 | chr2:178580041;178580040;178580039 | chr2:179444768;179444767;179444766 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/G | None | None | 0.001 | N | 0.243 | 0.139 | 0.107399877778 | gnomAD-4.0.0 | 1.59219E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.43303E-05 | 0 |
| A/P | rs4145333  |
-0.629 | None | N | 0.188 | 0.101 | None | gnomAD-2.1.1 | 9.98514E-01 | None | None | None | None | N | None | 9.86275E-01 | 9.9884E-01 | None | 1E+00 | 1E+00 | None | 1E+00 | None | 1E+00 | 9.99695E-01 | 9.99438E-01 |
| A/P | rs4145333 |
-0.629 | None | N | 0.188 | 0.101 | None | gnomAD-3.1.2 | 9.96021E-01 | None | None | None | None | N | None | 9.86485E-01 | 9.98754E-01 | 1E+00 | 1E+00 | 9.99805E-01 | None | 1E+00 | 9.90506E-01 | 9.99735E-01 | 1E+00 | 9.98088E-01 |
| A/P | rs4145333 |
-0.629 | None | N | 0.188 | 0.101 | None | 1000 genomes | 9.94609E-01 | None | None | None | None | N | None | 9.811E-01 | 9.971E-01 | None | None | 1E+00 | 1E+00 | None | None | None | 1E+00 | None |
| A/P | rs4145333 |
-0.629 | None | N | 0.188 | 0.101 | None | gnomAD-4.0.0 | 9.99095E-01 | None | None | None | None | N | None | 9.85665E-01 | 9.9885E-01 | None | 1E+00 | 9.99978E-01 | None | 1E+00 | 9.97851E-01 | 9.99807E-01 | 9.99978E-01 | 9.98847E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.273 | likely_benign | 0.2288 | benign | -0.852 | Destabilizing | 0.132 | N | 0.482 | neutral | None | None | None | None | N |
| A/D | 0.2156 | likely_benign | 0.1696 | benign | -0.721 | Destabilizing | 0.001 | N | 0.403 | neutral | N | 0.343184904 | None | None | N |
| A/E | 0.213 | likely_benign | 0.1803 | benign | -0.815 | Destabilizing | 0.001 | N | 0.387 | neutral | None | None | None | None | N |
| A/F | 0.2661 | likely_benign | 0.2239 | benign | -1.019 | Destabilizing | 0.009 | N | 0.439 | neutral | None | None | None | None | N |
| A/G | 0.0995 | likely_benign | 0.0926 | benign | -0.87 | Destabilizing | 0.001 | N | 0.243 | neutral | N | 0.392285573 | None | None | N |
| A/H | 0.3554 | ambiguous | 0.2766 | benign | -0.885 | Destabilizing | 0.041 | N | 0.556 | neutral | None | None | None | None | N |
| A/I | 0.1697 | likely_benign | 0.1392 | benign | -0.424 | Destabilizing | 0.001 | N | 0.345 | neutral | None | None | None | None | N |
| A/K | 0.3879 | ambiguous | 0.2967 | benign | -1.014 | Destabilizing | 0.001 | N | 0.366 | neutral | None | None | None | None | N |
| A/L | 0.1096 | likely_benign | 0.1005 | benign | -0.424 | Destabilizing | None | N | 0.175 | neutral | None | None | None | None | N |
| A/M | 0.1617 | likely_benign | 0.1371 | benign | -0.395 | Destabilizing | 0.021 | N | 0.506 | neutral | None | None | None | None | N |
| A/N | 0.1321 | likely_benign | 0.1105 | benign | -0.677 | Destabilizing | 0.001 | N | 0.384 | neutral | None | None | None | None | N |
| A/P | 0.083 | likely_benign | 0.0802 | benign | -0.477 | Destabilizing | None | N | 0.188 | neutral | N | 0.380279068 | None | None | N |
| A/Q | 0.2444 | likely_benign | 0.1978 | benign | -0.897 | Destabilizing | 0.009 | N | 0.379 | neutral | None | None | None | None | N |
| A/R | 0.4001 | ambiguous | 0.3107 | benign | -0.556 | Destabilizing | 0.004 | N | 0.352 | neutral | None | None | None | None | N |
| A/S | 0.0669 | likely_benign | 0.0657 | benign | -0.982 | Destabilizing | None | N | 0.123 | neutral | N | 0.347473216 | None | None | N |
| A/T | 0.066 | likely_benign | 0.0623 | benign | -0.98 | Destabilizing | None | N | 0.117 | neutral | N | 0.303605009 | None | None | N |
| A/V | 0.1135 | likely_benign | 0.1001 | benign | -0.477 | Destabilizing | None | N | 0.247 | neutral | N | 0.402174493 | None | None | N |
| A/W | 0.5792 | likely_pathogenic | 0.4948 | ambiguous | -1.229 | Destabilizing | 0.316 | N | 0.538 | neutral | None | None | None | None | N |
| A/Y | 0.3434 | ambiguous | 0.2776 | benign | -0.868 | Destabilizing | 0.018 | N | 0.471 | 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.