Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 31268 | 94027;94028;94029 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| N2AB | 29627 | 89104;89105;89106 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| N2A | 28700 | 86323;86324;86325 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| N2B | 22203 | 66832;66833;66834 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| Novex-1 | 22328 | 67207;67208;67209 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| Novex-2 | 22395 | 67408;67409;67410 | chr2:178547824;178547823;178547822 | chr2:179412551;179412550;179412549 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/N | None | None | 0.98 | N | 0.369 | 0.145 | 0.134241683229 | 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 |
| K/T | rs200766837  |
-0.002 | 0.997 | N | 0.389 | 0.433 | None | gnomAD-2.1.1 | 4.78653E-04 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 1.91892E-03 | 6.33456E-04 | 7.02445E-04 |
| K/T | rs200766837 |
-0.002 | 0.997 | N | 0.389 | 0.433 | None | gnomAD-3.1.2 | 1.83995E-04 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 1.13037E-03 | 0 | 2.20478E-04 | 0 | 4.78011E-04 |
| K/T | rs200766837 |
-0.002 | 0.997 | N | 0.389 | 0.433 | None |
Mihailov (2016)
| None |
IH 
|
het | None | None | N | Genetic analysis of single EST family; co-segregates within family (strongest candidate); incomplete penetrance (n = 5, 5 affected (total 9; 1 unaffected carrier, 1 condition in absence of variant)); not found in ethnic controls | None | None | None | None | None | None | None | None | None | None | None |
| K/T | rs200766837 |
-0.002 | 0.997 | N | 0.389 | 0.433 | None | gnomAD-4.0.0 | 3.15406E-04 | None | None | None | None | N | None | 1.33469E-05 | 0 | None | 0 | 0 | None | 1.85885E-03 | 0 | 3.06818E-04 | 0 | 4.32263E-04 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| K/A | 0.1828 | likely_benign | 0.1797 | benign | 0.03 | Stabilizing | 0.985 | D | 0.415 | neutral | None | None | None | None | N |
| K/C | 0.6346 | likely_pathogenic | 0.6588 | pathogenic | -0.318 | Destabilizing | 1.0 | D | 0.597 | neutral | None | None | None | None | N |
| K/D | 0.3554 | ambiguous | 0.3603 | ambiguous | -0.251 | Destabilizing | 0.171 | N | 0.307 | neutral | None | None | None | None | N |
| K/E | 0.1157 | likely_benign | 0.1084 | benign | -0.272 | Destabilizing | 0.4 | N | 0.259 | neutral | N | 0.416399292 | None | None | N |
| K/F | 0.7415 | likely_pathogenic | 0.768 | pathogenic | -0.335 | Destabilizing | 0.999 | D | 0.541 | neutral | None | None | None | None | N |
| K/G | 0.2455 | likely_benign | 0.2542 | benign | -0.09 | Destabilizing | 0.993 | D | 0.405 | neutral | None | None | None | None | N |
| K/H | 0.3221 | likely_benign | 0.3464 | ambiguous | -0.234 | Destabilizing | 1.0 | D | 0.414 | neutral | None | None | None | None | N |
| K/I | 0.3361 | likely_benign | 0.3438 | ambiguous | 0.26 | Stabilizing | 0.999 | D | 0.547 | neutral | N | 0.487878175 | None | None | N |
| K/L | 0.3055 | likely_benign | 0.3224 | benign | 0.26 | Stabilizing | 0.998 | D | 0.411 | neutral | None | None | None | None | N |
| K/M | 0.211 | likely_benign | 0.2127 | benign | -0.009 | Destabilizing | 1.0 | D | 0.451 | neutral | None | None | None | None | N |
| K/N | 0.2998 | likely_benign | 0.3085 | benign | 0.141 | Stabilizing | 0.98 | D | 0.369 | neutral | N | 0.424018698 | None | None | N |
| K/P | 0.3053 | likely_benign | 0.3055 | benign | 0.206 | Stabilizing | 0.999 | D | 0.412 | neutral | None | None | None | None | N |
| K/Q | 0.1277 | likely_benign | 0.1314 | benign | -0.023 | Destabilizing | 0.994 | D | 0.383 | neutral | N | 0.457555268 | None | None | N |
| K/R | 0.0785 | likely_benign | 0.079 | benign | -0.051 | Destabilizing | 0.98 | D | 0.395 | neutral | N | 0.44347125 | None | None | N |
| K/S | 0.2449 | likely_benign | 0.2511 | benign | -0.228 | Destabilizing | 0.985 | D | 0.38 | neutral | None | None | None | None | N |
| K/T | 0.1314 | likely_benign | 0.1342 | benign | -0.136 | Destabilizing | 0.997 | D | 0.389 | neutral | N | 0.449570503 | None | None | N |
| K/V | 0.2645 | likely_benign | 0.2675 | benign | 0.206 | Stabilizing | 0.998 | D | 0.443 | neutral | None | None | None | None | N |
| K/W | 0.6927 | likely_pathogenic | 0.7162 | pathogenic | -0.435 | Destabilizing | 1.0 | D | 0.621 | neutral | None | None | None | None | N |
| K/Y | 0.5997 | likely_pathogenic | 0.6286 | pathogenic | -0.078 | Destabilizing | 0.999 | D | 0.488 | 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.