Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27914 | 83965;83966;83967 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| N2AB | 26273 | 79042;79043;79044 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| N2A | 25346 | 76261;76262;76263 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| N2B | 18849 | 56770;56771;56772 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| Novex-1 | 18974 | 57145;57146;57147 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| Novex-2 | 19041 | 57346;57347;57348 | chr2:178562392;178562391;178562390 | chr2:179427119;179427118;179427117 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | rs188370772  |
-0.98 | 0.001 | N | 0.181 | 0.118 | None | gnomAD-2.1.1 | 8.28107E-04 | None | None | None | None | N | None | 8.60785E-03 | 1.42702E-04 | None | 0 | 0 | None | 3.34E-05 | None | 0 | 1.02095E-04 | 4.2517E-04 |
| T/A | rs188370772 |
-0.98 | 0.001 | N | 0.181 | 0.118 | None | gnomAD-3.1.2 | 2.41181E-03 | None | None | None | None | N | None | 8.20265E-03 | 8.5112E-04 | 0 | 0 | 0 | None | 0 | 0 | 1.32298E-04 | 2.07125E-04 | 1.91205E-03 |
| T/A | rs188370772 |
-0.98 | 0.001 | N | 0.181 | 0.118 | None | 1000 genomes | 3.19489E-03 | None | None | None | None | N | None | 1.13E-02 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| T/A | rs188370772 |
-0.98 | 0.001 | N | 0.181 | 0.118 | None | gnomAD-4.0.0 | 4.96972E-04 | None | None | None | None | N | None | 8.40852E-03 | 4.01553E-04 | None | 0 | 0 | None | 0 | 2.31405E-03 | 6.53026E-05 | 3.31316E-05 | 8.49468E-04 |
| T/K | rs1363810030 |
-0.79 | 0.351 | N | 0.422 | 0.191 | 0.246215685461 | gnomAD-2.1.1 | 4.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.94E-06 | 0 |
| T/K | rs1363810030 |
-0.79 | 0.351 | N | 0.422 | 0.191 | 0.246215685461 | gnomAD-4.0.0 | 2.05559E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.70006E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| T/A | 0.0692 | likely_benign | 0.0724 | benign | -0.851 | Destabilizing | 0.001 | N | 0.181 | neutral | N | 0.383842235 | None | None | N |
| T/C | 0.2728 | likely_benign | 0.3022 | benign | -0.521 | Destabilizing | 0.005 | N | 0.298 | neutral | None | None | None | None | N |
| T/D | 0.5027 | ambiguous | 0.5181 | ambiguous | -0.062 | Destabilizing | 0.418 | N | 0.455 | neutral | None | None | None | None | N |
| T/E | 0.4408 | ambiguous | 0.447 | ambiguous | -0.066 | Destabilizing | 0.418 | N | 0.423 | neutral | None | None | None | None | N |
| T/F | 0.2663 | likely_benign | 0.2798 | benign | -0.942 | Destabilizing | 0.716 | D | 0.488 | neutral | None | None | None | None | N |
| T/G | 0.2048 | likely_benign | 0.2325 | benign | -1.101 | Destabilizing | 0.129 | N | 0.399 | neutral | None | None | None | None | N |
| T/H | 0.3061 | likely_benign | 0.31 | benign | -1.399 | Destabilizing | 0.983 | D | 0.481 | neutral | None | None | None | None | N |
| T/I | 0.1719 | likely_benign | 0.1757 | benign | -0.279 | Destabilizing | 0.002 | N | 0.321 | neutral | N | 0.469516993 | None | None | N |
| T/K | 0.2975 | likely_benign | 0.3065 | benign | -0.707 | Destabilizing | 0.351 | N | 0.422 | neutral | N | 0.471863865 | None | None | N |
| T/L | 0.0883 | likely_benign | 0.0934 | benign | -0.279 | Destabilizing | 0.049 | N | 0.363 | neutral | None | None | None | None | N |
| T/M | 0.089 | likely_benign | 0.0883 | benign | -0.051 | Destabilizing | 0.716 | D | 0.486 | neutral | None | None | None | None | N |
| T/N | 0.1551 | likely_benign | 0.1654 | benign | -0.611 | Destabilizing | 0.418 | N | 0.437 | neutral | None | None | None | None | N |
| T/P | 0.5273 | ambiguous | 0.5053 | ambiguous | -0.438 | Destabilizing | 0.794 | D | 0.495 | neutral | N | 0.485737239 | None | None | N |
| T/Q | 0.2757 | likely_benign | 0.2765 | benign | -0.767 | Destabilizing | 0.836 | D | 0.494 | neutral | None | None | None | None | N |
| T/R | 0.2519 | likely_benign | 0.2607 | benign | -0.517 | Destabilizing | 0.655 | D | 0.505 | neutral | N | 0.484523731 | None | None | N |
| T/S | 0.0977 | likely_benign | 0.1031 | benign | -0.905 | Destabilizing | 0.009 | N | 0.175 | neutral | N | 0.431785324 | None | None | N |
| T/V | 0.1234 | likely_benign | 0.1289 | benign | -0.438 | Destabilizing | 0.01 | N | 0.178 | neutral | None | None | None | None | N |
| T/W | 0.7102 | likely_pathogenic | 0.7183 | pathogenic | -0.861 | Destabilizing | 0.983 | D | 0.517 | neutral | None | None | None | None | N |
| T/Y | 0.3458 | ambiguous | 0.3595 | ambiguous | -0.631 | Destabilizing | 0.836 | D | 0.49 | 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.