Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23558 | 70897;70898;70899 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| N2AB | 21917 | 65974;65975;65976 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| N2A | 20990 | 63193;63194;63195 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| N2B | 14493 | 43702;43703;43704 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| Novex-1 | 14618 | 44077;44078;44079 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| Novex-2 | 14685 | 44278;44279;44280 | chr2:178575460;178575459;178575458 | chr2:179440187;179440186;179440185 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/D | None | None | 0.936 | N | 0.407 | 0.456 | 0.286848849266 | gnomAD-4.0.0 | 2.05285E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.69868E-06 | 0 | 0 |
| H/Q | rs761993177  |
0.344 | 0.962 | N | 0.397 | 0.349 | 0.18274738541 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 0 | 0 |
| H/Q | rs761993177 |
0.344 | 0.962 | N | 0.397 | 0.349 | 0.18274738541 | gnomAD-4.0.0 | 6.84298E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 1.15947E-05 | 0 |
| H/R | rs765191581 |
-0.033 | 0.009 | N | 0.285 | 0.203 | 0.181679512989 | gnomAD-2.1.1 | 1.61E-05 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 2.67E-05 | 0 |
| H/R | rs765191581 |
-0.033 | 0.009 | N | 0.285 | 0.203 | 0.181679512989 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | I | None | 9.65E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| H/R | rs765191581 |
-0.033 | 0.009 | N | 0.285 | 0.203 | 0.181679512989 | gnomAD-4.0.0 | 8.05712E-06 | None | None | None | None | I | None | 6.67468E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 4.23855E-06 | 0 | 4.80415E-05 |
| H/Y | None | None | 0.96 | N | 0.427 | 0.374 | 0.26547132957 | gnomAD-4.0.0 | 6.84285E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.9956E-07 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| H/A | 0.6434 | likely_pathogenic | 0.6451 | pathogenic | 0.487 | Stabilizing | 0.901 | D | 0.495 | neutral | None | None | None | None | I |
| H/C | 0.3585 | ambiguous | 0.4014 | ambiguous | 0.684 | Stabilizing | 0.996 | D | 0.679 | prob.neutral | None | None | None | None | I |
| H/D | 0.4823 | ambiguous | 0.4788 | ambiguous | 0.031 | Stabilizing | 0.936 | D | 0.407 | neutral | N | 0.448749358 | None | None | I |
| H/E | 0.6362 | likely_pathogenic | 0.6407 | pathogenic | 0.023 | Stabilizing | 0.791 | D | 0.43 | neutral | None | None | None | None | I |
| H/F | 0.3223 | likely_benign | 0.3625 | ambiguous | 0.844 | Stabilizing | 0.991 | D | 0.465 | neutral | None | None | None | None | I |
| H/G | 0.6181 | likely_pathogenic | 0.6137 | pathogenic | 0.278 | Stabilizing | 0.901 | D | 0.493 | neutral | None | None | None | None | I |
| H/I | 0.6453 | likely_pathogenic | 0.6549 | pathogenic | 0.988 | Stabilizing | 0.963 | D | 0.639 | neutral | None | None | None | None | I |
| H/K | 0.6331 | likely_pathogenic | 0.6488 | pathogenic | 0.444 | Stabilizing | 0.646 | D | 0.49 | neutral | None | None | None | None | I |
| H/L | 0.3715 | ambiguous | 0.3447 | ambiguous | 0.988 | Stabilizing | 0.906 | D | 0.518 | neutral | N | 0.51095261 | None | None | I |
| H/M | 0.6673 | likely_pathogenic | 0.6766 | pathogenic | 0.746 | Stabilizing | 0.997 | D | 0.597 | neutral | None | None | None | None | I |
| H/N | 0.1885 | likely_benign | 0.1875 | benign | 0.437 | Stabilizing | 0.674 | D | 0.481 | neutral | N | 0.443074179 | None | None | I |
| H/P | 0.8673 | likely_pathogenic | 0.8352 | pathogenic | 0.845 | Stabilizing | 0.978 | D | 0.6 | neutral | N | 0.503373276 | None | None | I |
| H/Q | 0.4493 | ambiguous | 0.452 | ambiguous | 0.463 | Stabilizing | 0.962 | D | 0.397 | neutral | N | 0.502506485 | None | None | I |
| H/R | 0.3603 | ambiguous | 0.3589 | ambiguous | 0.008 | Stabilizing | 0.009 | N | 0.285 | neutral | N | 0.463892169 | None | None | I |
| H/S | 0.4245 | ambiguous | 0.4312 | ambiguous | 0.509 | Stabilizing | 0.901 | D | 0.467 | neutral | None | None | None | None | I |
| H/T | 0.5249 | ambiguous | 0.5321 | ambiguous | 0.59 | Stabilizing | 0.906 | D | 0.471 | neutral | None | None | None | None | I |
| H/V | 0.584 | likely_pathogenic | 0.5852 | pathogenic | 0.845 | Stabilizing | 0.964 | D | 0.637 | neutral | None | None | None | None | I |
| H/W | 0.4531 | ambiguous | 0.4626 | ambiguous | 0.704 | Stabilizing | 0.999 | D | 0.693 | prob.neutral | None | None | None | None | I |
| H/Y | 0.131 | likely_benign | 0.1354 | benign | 1.042 | Stabilizing | 0.96 | D | 0.427 | neutral | N | 0.442959536 | None | None | I |
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.