Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 20526 | 61801;61802;61803 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| N2AB | 18885 | 56878;56879;56880 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| N2A | 17958 | 54097;54098;54099 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| N2B | 11461 | 34606;34607;34608 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| Novex-1 | 11586 | 34981;34982;34983 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| Novex-2 | 11653 | 35182;35183;35184 | chr2:178590149;178590148;178590147 | chr2:179454876;179454875;179454874 |
| 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/S | rs1234706508  |
None | 0.326 | N | 0.373 | 0.302 | 0.587933254401 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| I/S | rs1234706508 |
None | 0.326 | N | 0.373 | 0.302 | 0.587933254401 | gnomAD-4.0.0 | 1.23984E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.69566E-06 | 0 | 0 |
| I/T | rs1234706508 |
None | None | N | 0.129 | 0.229 | 0.536568438421 | gnomAD-4.0.0 | 6.84439E-07 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99682E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.3015 | likely_benign | 0.2765 | benign | -1.822 | Destabilizing | 0.209 | N | 0.323 | neutral | None | None | None | None | N |
| I/C | 0.5529 | ambiguous | 0.4567 | ambiguous | -0.789 | Destabilizing | 0.965 | D | 0.403 | neutral | None | None | None | None | N |
| I/D | 0.5847 | likely_pathogenic | 0.5939 | pathogenic | -1.683 | Destabilizing | 0.818 | D | 0.457 | neutral | None | None | None | None | N |
| I/E | 0.45 | ambiguous | 0.4399 | ambiguous | -1.703 | Destabilizing | 0.561 | D | 0.432 | neutral | None | None | None | None | N |
| I/F | 0.1492 | likely_benign | 0.1252 | benign | -1.368 | Destabilizing | 0.772 | D | 0.343 | neutral | N | 0.502139204 | None | None | N |
| I/G | 0.5461 | ambiguous | 0.5139 | ambiguous | -2.129 | Highly Destabilizing | 0.561 | D | 0.445 | neutral | None | None | None | None | N |
| I/H | 0.2811 | likely_benign | 0.2563 | benign | -1.466 | Destabilizing | 0.991 | D | 0.443 | neutral | None | None | None | None | N |
| I/K | 0.2443 | likely_benign | 0.2538 | benign | -1.329 | Destabilizing | 0.561 | D | 0.425 | neutral | None | None | None | None | N |
| I/L | 0.1133 | likely_benign | 0.0924 | benign | -1.041 | Destabilizing | 0.001 | N | 0.093 | neutral | N | 0.437799724 | None | None | N |
| I/M | 0.1238 | likely_benign | 0.1115 | benign | -0.614 | Destabilizing | 0.772 | D | 0.391 | neutral | N | 0.480859855 | None | None | N |
| I/N | 0.1511 | likely_benign | 0.1627 | benign | -0.999 | Destabilizing | 0.772 | D | 0.463 | neutral | N | 0.465717044 | None | None | N |
| I/P | 0.7647 | likely_pathogenic | 0.7782 | pathogenic | -1.273 | Destabilizing | 0.901 | D | 0.467 | neutral | None | None | None | None | N |
| I/Q | 0.262 | likely_benign | 0.239 | benign | -1.239 | Destabilizing | 0.901 | D | 0.467 | neutral | None | None | None | None | N |
| I/R | 0.1987 | likely_benign | 0.2138 | benign | -0.654 | Destabilizing | 0.818 | D | 0.47 | neutral | None | None | None | None | N |
| I/S | 0.1869 | likely_benign | 0.193 | benign | -1.485 | Destabilizing | 0.326 | N | 0.373 | neutral | N | 0.442242752 | None | None | N |
| I/T | 0.1985 | likely_benign | 0.1859 | benign | -1.409 | Destabilizing | None | N | 0.129 | neutral | N | 0.427003941 | None | None | N |
| I/V | 0.1134 | likely_benign | 0.0945 | benign | -1.273 | Destabilizing | 0.001 | N | 0.132 | neutral | N | 0.46231138 | None | None | N |
| I/W | 0.6937 | likely_pathogenic | 0.6124 | pathogenic | -1.47 | Destabilizing | 0.991 | D | 0.47 | neutral | None | None | None | None | N |
| I/Y | 0.3756 | ambiguous | 0.3442 | ambiguous | -1.297 | Destabilizing | 0.901 | D | 0.411 | 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.