Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22800 | 68623;68624;68625 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| N2AB | 21159 | 63700;63701;63702 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| N2A | 20232 | 60919;60920;60921 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| N2B | 13735 | 41428;41429;41430 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| Novex-1 | 13860 | 41803;41804;41805 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| Novex-2 | 13927 | 42004;42005;42006 | chr2:178578117;178578116;178578115 | chr2:179442844;179442843;179442842 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/R | None | None | 0.873 | N | 0.378 | 0.373 | 0.565865824572 | gnomAD-4.0.0 | 1.3692E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.79994E-06 | 0 | 0 |
| M/T | rs751870146  |
-0.048 | 0.285 | N | 0.333 | 0.304 | 0.636921891668 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 1.11707E-04 | None | 0 | None | 0 | 0 | 0 |
| M/T | rs751870146 |
-0.048 | 0.285 | N | 0.333 | 0.304 | 0.636921891668 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 3.86847E-04 | None | 0 | 0 | 0 | 0 | 0 |
| M/T | rs751870146 |
-0.048 | 0.285 | N | 0.333 | 0.304 | 0.636921891668 | gnomAD-4.0.0 | 1.86008E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 4.46449E-05 | None | 0 | 0 | 8.48038E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.3423 | ambiguous | 0.3037 | benign | -0.881 | Destabilizing | 0.103 | N | 0.264 | neutral | None | None | None | None | I |
| M/C | 0.656 | likely_pathogenic | 0.664 | pathogenic | -0.831 | Destabilizing | 0.965 | D | 0.352 | neutral | None | None | None | None | I |
| M/D | 0.7151 | likely_pathogenic | 0.7286 | pathogenic | -0.182 | Destabilizing | 0.965 | D | 0.389 | neutral | None | None | None | None | I |
| M/E | 0.4572 | ambiguous | 0.476 | ambiguous | -0.172 | Destabilizing | 0.722 | D | 0.363 | neutral | None | None | None | None | I |
| M/F | 0.3405 | ambiguous | 0.3303 | benign | -0.231 | Destabilizing | 0.561 | D | 0.309 | neutral | None | None | None | None | I |
| M/G | 0.4106 | ambiguous | 0.3879 | ambiguous | -1.112 | Destabilizing | 0.722 | D | 0.386 | neutral | None | None | None | None | I |
| M/H | 0.4361 | ambiguous | 0.4776 | ambiguous | -0.151 | Destabilizing | 0.991 | D | 0.332 | neutral | None | None | None | None | I |
| M/I | 0.4068 | ambiguous | 0.3572 | ambiguous | -0.324 | Destabilizing | 0.08 | N | 0.152 | neutral | N | 0.440962168 | None | None | I |
| M/K | 0.2168 | likely_benign | 0.2428 | benign | -0.099 | Destabilizing | 0.662 | D | 0.351 | neutral | N | 0.399422189 | None | None | I |
| M/L | 0.1315 | likely_benign | 0.1203 | benign | -0.324 | Destabilizing | 0.036 | N | 0.135 | neutral | N | 0.421029613 | None | None | I |
| M/N | 0.353 | ambiguous | 0.336 | benign | -0.104 | Destabilizing | 0.965 | D | 0.367 | neutral | None | None | None | None | I |
| M/P | 0.6971 | likely_pathogenic | 0.6764 | pathogenic | -0.483 | Destabilizing | 0.965 | D | 0.377 | neutral | None | None | None | None | I |
| M/Q | 0.203 | likely_benign | 0.2256 | benign | -0.179 | Destabilizing | 0.965 | D | 0.314 | neutral | None | None | None | None | I |
| M/R | 0.2369 | likely_benign | 0.2653 | benign | 0.387 | Stabilizing | 0.873 | D | 0.378 | neutral | N | 0.391072065 | None | None | I |
| M/S | 0.2996 | likely_benign | 0.2819 | benign | -0.562 | Destabilizing | 0.722 | D | 0.342 | neutral | None | None | None | None | I |
| M/T | 0.2075 | likely_benign | 0.2011 | benign | -0.446 | Destabilizing | 0.285 | N | 0.333 | neutral | N | 0.369155211 | None | None | I |
| M/V | 0.1238 | likely_benign | 0.1105 | benign | -0.483 | Destabilizing | None | N | 0.128 | neutral | N | 0.406214876 | None | None | I |
| M/W | 0.642 | likely_pathogenic | 0.6681 | pathogenic | -0.23 | Destabilizing | 0.991 | D | 0.356 | neutral | None | None | None | None | I |
| M/Y | 0.5322 | ambiguous | 0.5501 | ambiguous | -0.143 | Destabilizing | 0.901 | D | 0.388 | neutral | None | None | 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.