Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 15218 | 45877;45878;45879 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| N2AB | 13577 | 40954;40955;40956 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| N2A | 12650 | 38173;38174;38175 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| N2B | 6153 | 18682;18683;18684 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| Novex-1 | 6278 | 19057;19058;19059 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| Novex-2 | 6345 | 19258;19259;19260 | chr2:178620958;178620957;178620956 | chr2:179485685;179485684;179485683 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs548035065  |
0.087 | 0.002 | N | 0.217 | 0.092 | 0.165133752707 | gnomAD-2.1.1 | 8.09E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 3.28E-05 | None | 0 | 8.96E-06 | 0 |
| R/Q | rs548035065 |
0.087 | 0.002 | N | 0.217 | 0.092 | 0.165133752707 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 4.83E-05 | 6.57E-05 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| R/Q | rs548035065 |
0.087 | 0.002 | N | 0.217 | 0.092 | 0.165133752707 | 1000 genomes | 1.99681E-04 | None | None | None | None | N | None | 0 | 1.4E-03 | None | None | 0 | 0 | None | None | None | 0 | None |
| R/Q | rs548035065 |
0.087 | 0.002 | N | 0.217 | 0.092 | 0.165133752707 | gnomAD-4.0.0 | 7.44314E-06 | None | None | None | None | N | None | 2.67123E-05 | 1.67185E-05 | None | 0 | 0 | None | 0 | 1.65508E-04 | 3.39238E-06 | 2.19833E-05 | 3.20677E-05 |
| R/W | rs371621174 |
-0.489 | 0.964 | N | 0.331 | 0.322 | None | gnomAD-2.1.1 | 4.05E-05 | None | None | None | None | N | None | 6.48E-05 | 2.92E-05 | None | 0 | 0 | None | 3.28E-05 | None | 9.3E-05 | 3.58E-05 | 1.67336E-04 |
| R/W | rs371621174 |
-0.489 | 0.964 | N | 0.331 | 0.322 | None | gnomAD-3.1.2 | 4.61E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 7.37E-05 | 0 | 4.78927E-04 |
| R/W | rs371621174 |
-0.489 | 0.964 | N | 0.331 | 0.322 | None | gnomAD-4.0.0 | 4.5905E-05 | None | None | None | None | N | None | 4.01456E-05 | 3.3456E-05 | None | 3.38364E-05 | 0 | None | 1.56377E-05 | 0 | 5.08867E-05 | 1.09931E-05 | 9.62371E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.2308 | likely_benign | 0.2255 | benign | -0.187 | Destabilizing | 0.007 | N | 0.269 | neutral | None | None | None | None | N |
| R/C | 0.1799 | likely_benign | 0.1804 | benign | -0.413 | Destabilizing | 0.864 | D | 0.325 | neutral | None | None | None | None | N |
| R/D | 0.5792 | likely_pathogenic | 0.5356 | ambiguous | -0.041 | Destabilizing | 0.016 | N | 0.309 | neutral | None | None | None | None | N |
| R/E | 0.2512 | likely_benign | 0.2324 | benign | 0.074 | Stabilizing | None | N | 0.162 | neutral | None | None | None | None | N |
| R/F | 0.4176 | ambiguous | 0.4173 | ambiguous | -0.109 | Destabilizing | 0.628 | D | 0.363 | neutral | None | None | None | None | N |
| R/G | 0.2328 | likely_benign | 0.1969 | benign | -0.461 | Destabilizing | 0.058 | N | 0.317 | neutral | N | 0.510231113 | None | None | N |
| R/H | 0.0943 | likely_benign | 0.106 | benign | -0.82 | Destabilizing | 0.356 | N | 0.363 | neutral | None | None | None | None | N |
| R/I | 0.1487 | likely_benign | 0.1463 | benign | 0.526 | Stabilizing | 0.136 | N | 0.471 | neutral | None | None | None | None | N |
| R/K | 0.0794 | likely_benign | 0.0809 | benign | -0.327 | Destabilizing | None | N | 0.173 | neutral | None | None | None | None | N |
| R/L | 0.1775 | likely_benign | 0.1795 | benign | 0.526 | Stabilizing | 0.058 | N | 0.366 | neutral | N | 0.48731109 | None | None | N |
| R/M | 0.1717 | likely_benign | 0.1638 | benign | -0.063 | Destabilizing | 0.628 | D | 0.365 | neutral | None | None | None | None | N |
| R/N | 0.3734 | ambiguous | 0.362 | ambiguous | -0.116 | Destabilizing | 0.031 | N | 0.361 | neutral | None | None | None | None | N |
| R/P | 0.6586 | likely_pathogenic | 0.6172 | pathogenic | 0.311 | Stabilizing | None | N | 0.23 | neutral | N | 0.511180986 | None | None | N |
| R/Q | 0.0986 | likely_benign | 0.1 | benign | -0.156 | Destabilizing | 0.002 | N | 0.217 | neutral | N | 0.422498498 | None | None | N |
| R/S | 0.3014 | likely_benign | 0.2807 | benign | -0.585 | Destabilizing | 0.016 | N | 0.319 | neutral | None | None | None | None | N |
| R/T | 0.1066 | likely_benign | 0.1123 | benign | -0.304 | Destabilizing | 0.031 | N | 0.383 | neutral | None | None | None | None | N |
| R/V | 0.1869 | likely_benign | 0.1969 | benign | 0.311 | Stabilizing | 0.031 | N | 0.428 | neutral | None | None | None | None | N |
| R/W | 0.1831 | likely_benign | 0.1624 | benign | 0.002 | Stabilizing | 0.964 | D | 0.331 | neutral | N | 0.512062491 | None | None | N |
| R/Y | 0.3468 | ambiguous | 0.3506 | ambiguous | 0.352 | Stabilizing | 0.628 | D | 0.427 | 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.