Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19435 | 58528;58529;58530 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| N2AB | 17794 | 53605;53606;53607 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| N2A | 16867 | 50824;50825;50826 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| N2B | 10370 | 31333;31334;31335 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| Novex-1 | 10495 | 31708;31709;31710 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| Novex-2 | 10562 | 31909;31910;31911 | chr2:178594090;178594089;178594088 | chr2:179458817;179458816;179458815 |
| 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 | 0.003 | N | 0.199 | 0.105 | 0.37281450598 | gnomAD-4.0.0 | 6.84325E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99554E-07 | 0 | 0 |
| I/M | None | None | 0.901 | D | 0.547 | 0.225 | 0.486282253068 | gnomAD-4.0.0 | 1.59189E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85915E-06 | 0 | 0 |
| I/T | rs935570365  |
None | 0.722 | N | 0.597 | 0.437 | 0.738272365714 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.3125E-06 | 0 | 0 |
| I/V | rs749402480 |
-1.299 | 0.19 | N | 0.406 | 0.083 | 0.336155897331 | gnomAD-2.1.1 | 4.03E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.9E-06 | 0 |
| I/V | rs749402480 |
-1.299 | 0.19 | N | 0.406 | 0.083 | 0.336155897331 | gnomAD-4.0.0 | 2.7373E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 3.59822E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.5855 | likely_pathogenic | 0.5989 | pathogenic | -2.038 | Highly Destabilizing | 0.775 | D | 0.487 | neutral | None | None | None | None | N |
| I/C | 0.6513 | likely_pathogenic | 0.6465 | pathogenic | -1.15 | Destabilizing | 0.996 | D | 0.654 | neutral | None | None | None | None | N |
| I/D | 0.8919 | likely_pathogenic | 0.9109 | pathogenic | -1.649 | Destabilizing | 0.987 | D | 0.771 | deleterious | None | None | None | None | N |
| I/E | 0.7172 | likely_pathogenic | 0.7365 | pathogenic | -1.561 | Destabilizing | 0.961 | D | 0.763 | deleterious | None | None | None | None | N |
| I/F | 0.136 | likely_benign | 0.1583 | benign | -1.288 | Destabilizing | 0.858 | D | 0.545 | neutral | None | None | None | None | N |
| I/G | 0.7987 | likely_pathogenic | 0.8162 | pathogenic | -2.458 | Highly Destabilizing | 0.961 | D | 0.742 | deleterious | None | None | None | None | N |
| I/H | 0.5542 | ambiguous | 0.5796 | pathogenic | -1.69 | Destabilizing | 0.996 | D | 0.76 | deleterious | None | None | None | None | N |
| I/K | 0.3886 | ambiguous | 0.3883 | ambiguous | -1.457 | Destabilizing | 0.949 | D | 0.745 | deleterious | N | 0.506157804 | None | None | N |
| I/L | 0.1225 | likely_benign | 0.1272 | benign | -0.904 | Destabilizing | 0.003 | N | 0.199 | neutral | N | 0.472203086 | None | None | N |
| I/M | 0.1221 | likely_benign | 0.1344 | benign | -0.672 | Destabilizing | 0.901 | D | 0.547 | neutral | D | 0.527480366 | None | None | N |
| I/N | 0.4993 | ambiguous | 0.5443 | ambiguous | -1.379 | Destabilizing | 0.987 | D | 0.776 | deleterious | None | None | None | None | N |
| I/P | 0.8978 | likely_pathogenic | 0.9095 | pathogenic | -1.254 | Destabilizing | 0.987 | D | 0.773 | deleterious | None | None | None | None | N |
| I/Q | 0.4738 | ambiguous | 0.4959 | ambiguous | -1.451 | Destabilizing | 0.987 | D | 0.771 | deleterious | None | None | None | None | N |
| I/R | 0.3016 | likely_benign | 0.2948 | benign | -0.944 | Destabilizing | 0.949 | D | 0.777 | deleterious | N | 0.492421642 | None | None | N |
| I/S | 0.5079 | ambiguous | 0.5352 | ambiguous | -2.045 | Highly Destabilizing | 0.961 | D | 0.661 | neutral | None | None | None | None | N |
| I/T | 0.418 | ambiguous | 0.4288 | ambiguous | -1.829 | Destabilizing | 0.722 | D | 0.597 | neutral | N | 0.4890146 | None | None | N |
| I/V | 0.1043 | likely_benign | 0.0972 | benign | -1.254 | Destabilizing | 0.19 | N | 0.406 | neutral | N | 0.494671727 | None | None | N |
| I/W | 0.6131 | likely_pathogenic | 0.6372 | pathogenic | -1.474 | Destabilizing | 0.996 | D | 0.746 | deleterious | None | None | None | None | N |
| I/Y | 0.4629 | ambiguous | 0.488 | ambiguous | -1.231 | Destabilizing | 0.961 | D | 0.678 | prob.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.