Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 14384 | 43375;43376;43377 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| N2AB | 12743 | 38452;38453;38454 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| N2A | 11816 | 35671;35672;35673 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| N2B | 5319 | 16180;16181;16182 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| Novex-1 | 5444 | 16555;16556;16557 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| Novex-2 | 5511 | 16756;16757;16758 | chr2:178632981;178632980;178632979 | chr2:179497708;179497707;179497706 |
| 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/I | rs1454108479  |
-0.634 | 0.936 | N | 0.399 | 0.236 | 0.331619326243 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.92E-06 | 0 |
| M/I | rs1454108479 |
-0.634 | 0.936 | N | 0.399 | 0.236 | 0.331619326243 | gnomAD-4.0.0 | 1.59252E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.02663E-05 |
| M/V | rs1450926397 |
None | 0.665 | N | 0.362 | 0.203 | 0.315903272564 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| M/V | rs1450926397 |
None | 0.665 | N | 0.362 | 0.203 | 0.315903272564 | gnomAD-4.0.0 | 2.03004E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.40996E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| M/A | 0.7575 | likely_pathogenic | 0.6935 | pathogenic | -1.814 | Destabilizing | 0.565 | D | 0.369 | neutral | None | None | None | None | N |
| M/C | 0.9472 | likely_pathogenic | 0.9382 | pathogenic | -1.449 | Destabilizing | 0.996 | D | 0.521 | neutral | None | None | None | None | N |
| M/D | 0.7073 | likely_pathogenic | 0.6658 | pathogenic | -0.396 | Destabilizing | 0.759 | D | 0.489 | neutral | None | None | None | None | N |
| M/E | 0.6517 | likely_pathogenic | 0.6062 | pathogenic | -0.334 | Destabilizing | 0.394 | N | 0.347 | neutral | None | None | None | None | N |
| M/F | 0.5138 | ambiguous | 0.4873 | ambiguous | -0.699 | Destabilizing | 0.986 | D | 0.483 | neutral | None | None | None | None | N |
| M/G | 0.9015 | likely_pathogenic | 0.8713 | pathogenic | -2.167 | Highly Destabilizing | 0.864 | D | 0.471 | neutral | None | None | None | None | N |
| M/H | 0.7013 | likely_pathogenic | 0.6467 | pathogenic | -1.14 | Destabilizing | 0.957 | D | 0.561 | neutral | None | None | None | None | N |
| M/I | 0.6709 | likely_pathogenic | 0.6037 | pathogenic | -0.884 | Destabilizing | 0.936 | D | 0.399 | neutral | N | 0.476134984 | None | None | N |
| M/K | 0.4932 | ambiguous | 0.4221 | ambiguous | -0.586 | Destabilizing | 0.329 | N | 0.37 | neutral | N | 0.473295294 | None | None | N |
| M/L | 0.2417 | likely_benign | 0.2228 | benign | -0.884 | Destabilizing | 0.299 | N | 0.252 | neutral | N | 0.410369972 | None | None | N |
| M/N | 0.6309 | likely_pathogenic | 0.5595 | ambiguous | -0.54 | Destabilizing | 0.864 | D | 0.514 | neutral | None | None | None | None | N |
| M/P | 0.9806 | likely_pathogenic | 0.978 | pathogenic | -1.167 | Destabilizing | 0.951 | D | 0.587 | neutral | None | None | None | None | N |
| M/Q | 0.3312 | likely_benign | 0.296 | benign | -0.546 | Destabilizing | 0.017 | N | 0.183 | neutral | None | None | None | None | N |
| M/R | 0.5824 | likely_pathogenic | 0.5121 | ambiguous | -0.162 | Destabilizing | 0.704 | D | 0.52 | neutral | N | 0.408840327 | None | None | N |
| M/S | 0.6813 | likely_pathogenic | 0.6212 | pathogenic | -1.222 | Destabilizing | 0.565 | D | 0.4 | neutral | None | None | None | None | N |
| M/T | 0.5759 | likely_pathogenic | 0.4987 | ambiguous | -1.032 | Destabilizing | 0.828 | D | 0.488 | neutral | N | 0.474240292 | None | None | N |
| M/V | 0.2947 | likely_benign | 0.2646 | benign | -1.167 | Destabilizing | 0.665 | D | 0.362 | neutral | N | 0.476134984 | None | None | N |
| M/W | 0.7745 | likely_pathogenic | 0.7591 | pathogenic | -0.633 | Destabilizing | 0.996 | D | 0.506 | neutral | None | None | None | None | N |
| M/Y | 0.7583 | likely_pathogenic | 0.7192 | pathogenic | -0.667 | Destabilizing | 0.986 | D | 0.644 | 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.