Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23222 | 69889;69890;69891 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| N2AB | 21581 | 64966;64967;64968 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| N2A | 20654 | 62185;62186;62187 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| N2B | 14157 | 42694;42695;42696 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| Novex-1 | 14282 | 43069;43070;43071 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| Novex-2 | 14349 | 43270;43271;43272 | chr2:178576580;178576579;178576578 | chr2:179441307;179441306;179441305 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/L | None | None | 0.007 | N | 0.269 | 0.048 | 0.128392430309 | gnomAD-4.0.0 | 4.79004E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.39731E-06 | 0 | 1.65695E-05 |
| I/T | rs1223761195  |
-1.006 | 0.351 | N | 0.507 | 0.179 | 0.440810947182 | gnomAD-2.1.1 | 3.19E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 6.52742E-04 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1223761195 |
-1.006 | 0.351 | N | 0.507 | 0.179 | 0.440810947182 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93874E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/T | rs1223761195 |
-1.006 | 0.351 | N | 0.507 | 0.179 | 0.440810947182 | gnomAD-4.0.0 | 6.57462E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 1.93874E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs766103673 |
-1.119 | None | N | 0.207 | 0.031 | 0.192905019026 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.91E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.1446 | likely_benign | 0.1673 | benign | -1.343 | Destabilizing | 0.129 | N | 0.493 | neutral | None | None | None | None | N |
| I/C | 0.4725 | ambiguous | 0.5049 | ambiguous | -0.728 | Destabilizing | 0.836 | D | 0.563 | neutral | None | None | None | None | N |
| I/D | 0.6311 | likely_pathogenic | 0.6911 | pathogenic | -0.868 | Destabilizing | 0.94 | D | 0.6 | neutral | None | None | None | None | N |
| I/E | 0.4831 | ambiguous | 0.5353 | ambiguous | -0.942 | Destabilizing | 0.593 | D | 0.599 | neutral | None | None | None | None | N |
| I/F | 0.1323 | likely_benign | 0.1564 | benign | -1.236 | Destabilizing | 0.001 | N | 0.231 | neutral | N | 0.421376329 | None | None | N |
| I/G | 0.4844 | ambiguous | 0.5559 | ambiguous | -1.573 | Destabilizing | 0.593 | D | 0.559 | neutral | None | None | None | None | N |
| I/H | 0.4399 | ambiguous | 0.4893 | ambiguous | -0.759 | Destabilizing | 0.94 | D | 0.586 | neutral | None | None | None | None | N |
| I/K | 0.3351 | likely_benign | 0.3478 | ambiguous | -0.691 | Destabilizing | 0.418 | N | 0.603 | neutral | None | None | None | None | N |
| I/L | 0.0957 | likely_benign | 0.1009 | benign | -0.824 | Destabilizing | 0.007 | N | 0.269 | neutral | N | 0.394381729 | None | None | N |
| I/M | 0.0956 | likely_benign | 0.1047 | benign | -0.514 | Destabilizing | 0.021 | N | 0.307 | neutral | N | 0.464628461 | None | None | N |
| I/N | 0.2804 | likely_benign | 0.3202 | benign | -0.415 | Destabilizing | 0.794 | D | 0.593 | neutral | N | 0.499258323 | None | None | N |
| I/P | 0.3084 | likely_benign | 0.3713 | ambiguous | -0.964 | Destabilizing | 0.94 | D | 0.601 | neutral | None | None | None | None | N |
| I/Q | 0.3562 | ambiguous | 0.3978 | ambiguous | -0.729 | Destabilizing | 0.836 | D | 0.593 | neutral | None | None | None | None | N |
| I/R | 0.2491 | likely_benign | 0.2831 | benign | -0.007 | Destabilizing | 0.836 | D | 0.593 | neutral | None | None | None | None | N |
| I/S | 0.1996 | likely_benign | 0.2331 | benign | -0.946 | Destabilizing | 0.351 | N | 0.574 | neutral | N | 0.450216369 | None | None | N |
| I/T | 0.091 | likely_benign | 0.0947 | benign | -0.913 | Destabilizing | 0.351 | N | 0.507 | neutral | N | 0.427590226 | None | None | N |
| I/V | 0.0595 | likely_benign | 0.0591 | benign | -0.964 | Destabilizing | None | N | 0.207 | neutral | N | 0.4100819 | None | None | N |
| I/W | 0.6379 | likely_pathogenic | 0.6979 | pathogenic | -1.206 | Destabilizing | 0.983 | D | 0.588 | neutral | None | None | None | None | N |
| I/Y | 0.4274 | ambiguous | 0.4801 | ambiguous | -0.976 | Destabilizing | 0.264 | N | 0.514 | 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.