Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27539 | 82840;82841;82842 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| N2AB | 25898 | 77917;77918;77919 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| N2A | 24971 | 75136;75137;75138 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| N2B | 18474 | 55645;55646;55647 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| Novex-1 | 18599 | 56020;56021;56022 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| Novex-2 | 18666 | 56221;56222;56223 | chr2:178563517;178563516;178563515 | chr2:179428244;179428243;179428242 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/C | rs727503556  |
-0.343 | 0.987 | N | 0.489 | 0.305 | None | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | N | None | 1.93798E-04 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| S/C | rs727503556 |
-0.343 | 0.987 | N | 0.489 | 0.305 | None | gnomAD-3.1.2 | 1.31E-05 | None | None | None | None | N | None | 4.83E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/C | rs727503556 |
-0.343 | 0.987 | N | 0.489 | 0.305 | None | gnomAD-4.0.0 | 4.9577E-06 | None | None | None | None | N | None | 1.06792E-04 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| S/T | None | None | 0.003 | N | 0.145 | 0.073 | 0.148003135375 | gnomAD-4.0.0 | 1.20032E-06 | None | None | None | None | N | None | 0 | 0 | None | 1.94099E-04 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.0825 | likely_benign | 0.0877 | benign | -0.752 | Destabilizing | 0.166 | N | 0.353 | neutral | N | 0.494911296 | None | None | N |
| S/C | 0.0815 | likely_benign | 0.08 | benign | -0.387 | Destabilizing | 0.987 | D | 0.489 | neutral | N | 0.471902217 | None | None | N |
| S/D | 0.2646 | likely_benign | 0.2948 | benign | -1.385 | Destabilizing | 0.561 | D | 0.427 | neutral | None | None | None | None | N |
| S/E | 0.4001 | ambiguous | 0.4348 | ambiguous | -1.215 | Destabilizing | 0.561 | D | 0.418 | neutral | None | None | None | None | N |
| S/F | 0.1194 | likely_benign | 0.1244 | benign | -0.414 | Destabilizing | 0.001 | N | 0.32 | neutral | N | 0.459414642 | None | None | N |
| S/G | 0.1145 | likely_benign | 0.1133 | benign | -1.135 | Destabilizing | 0.345 | N | 0.393 | neutral | None | None | None | None | N |
| S/H | 0.2417 | likely_benign | 0.2476 | benign | -1.508 | Destabilizing | 0.009 | N | 0.299 | neutral | None | None | None | None | N |
| S/I | 0.1463 | likely_benign | 0.1523 | benign | 0.221 | Stabilizing | 0.39 | N | 0.467 | neutral | None | None | None | None | N |
| S/K | 0.6614 | likely_pathogenic | 0.6812 | pathogenic | -0.522 | Destabilizing | 0.561 | D | 0.429 | neutral | None | None | None | None | N |
| S/L | 0.099 | likely_benign | 0.1042 | benign | 0.221 | Stabilizing | 0.209 | N | 0.415 | neutral | None | None | None | None | N |
| S/M | 0.1924 | likely_benign | 0.1967 | benign | 0.23 | Stabilizing | 0.901 | D | 0.511 | neutral | None | None | None | None | N |
| S/N | 0.1166 | likely_benign | 0.1222 | benign | -1.081 | Destabilizing | 0.561 | D | 0.435 | neutral | None | None | None | None | N |
| S/P | 0.4128 | ambiguous | 0.5108 | ambiguous | -0.07 | Destabilizing | 0.873 | D | 0.496 | neutral | N | 0.50774452 | None | None | N |
| S/Q | 0.4 | ambiguous | 0.4048 | ambiguous | -0.822 | Destabilizing | 0.901 | D | 0.528 | neutral | None | None | None | None | N |
| S/R | 0.552 | ambiguous | 0.5694 | pathogenic | -0.871 | Destabilizing | 0.818 | D | 0.493 | neutral | None | None | None | None | N |
| S/T | 0.0894 | likely_benign | 0.0942 | benign | -0.76 | Destabilizing | 0.003 | N | 0.145 | neutral | N | 0.425531355 | None | None | N |
| S/V | 0.1428 | likely_benign | 0.1567 | benign | -0.07 | Destabilizing | 0.39 | N | 0.431 | neutral | None | None | None | None | N |
| S/W | 0.2191 | likely_benign | 0.2276 | benign | -0.753 | Destabilizing | 0.991 | D | 0.553 | neutral | None | None | None | None | N |
| S/Y | 0.1135 | likely_benign | 0.119 | benign | -0.337 | Destabilizing | 0.013 | N | 0.352 | neutral | N | 0.514441206 | 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.