Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 17929 | 54010;54011;54012 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| N2AB | 16288 | 49087;49088;49089 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| N2A | 15361 | 46306;46307;46308 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| N2B | 8864 | 26815;26816;26817 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| Novex-1 | 8989 | 27190;27191;27192 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| Novex-2 | 9056 | 27391;27392;27393 | chr2:178605510;178605509;178605508 | chr2:179470237;179470236;179470235 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/G | None | None | 0.999 | N | 0.617 | 0.541 | 0.472023113445 | gnomAD-4.0.0 | 1.59432E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86462E-06 | 0 | 0 |
| E/K | rs201052994  |
-0.245 | 0.998 | D | 0.641 | 0.354 | 0.338110398507 | gnomAD-2.1.1 | 8.06E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| E/K | rs201052994 |
-0.245 | 0.998 | D | 0.641 | 0.354 | 0.338110398507 | gnomAD-3.1.2 | 1.98E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 4.42E-05 | 0 | 0 |
| E/K | rs201052994 |
-0.245 | 0.998 | D | 0.641 | 0.354 | 0.338110398507 | gnomAD-4.0.0 | 1.0544E-05 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 1.44203E-05 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| E/A | 0.3112 | likely_benign | 0.3259 | benign | -0.684 | Destabilizing | 0.998 | D | 0.633 | neutral | N | 0.501047834 | None | None | N |
| E/C | 0.946 | likely_pathogenic | 0.943 | pathogenic | -0.339 | Destabilizing | 1.0 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/D | 0.4004 | ambiguous | 0.4007 | ambiguous | -0.977 | Destabilizing | 0.434 | N | 0.201 | neutral | N | 0.520444458 | None | None | N |
| E/F | 0.9507 | likely_pathogenic | 0.9478 | pathogenic | -0.532 | Destabilizing | 1.0 | D | 0.69 | prob.neutral | None | None | None | None | N |
| E/G | 0.457 | ambiguous | 0.4739 | ambiguous | -0.987 | Destabilizing | 0.999 | D | 0.617 | neutral | N | 0.482613412 | None | None | N |
| E/H | 0.8547 | likely_pathogenic | 0.8462 | pathogenic | -0.854 | Destabilizing | 1.0 | D | 0.659 | neutral | None | None | None | None | N |
| E/I | 0.6683 | likely_pathogenic | 0.6753 | pathogenic | 0.117 | Stabilizing | 1.0 | D | 0.706 | prob.neutral | None | None | None | None | N |
| E/K | 0.5178 | ambiguous | 0.4978 | ambiguous | -0.637 | Destabilizing | 0.998 | D | 0.641 | neutral | D | 0.524868843 | None | None | N |
| E/L | 0.8113 | likely_pathogenic | 0.8098 | pathogenic | 0.117 | Stabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/M | 0.7822 | likely_pathogenic | 0.7816 | pathogenic | 0.518 | Stabilizing | 1.0 | D | 0.658 | neutral | None | None | None | None | N |
| E/N | 0.6448 | likely_pathogenic | 0.6349 | pathogenic | -0.841 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | N |
| E/P | 0.6085 | likely_pathogenic | 0.6017 | pathogenic | -0.128 | Destabilizing | 1.0 | D | 0.654 | neutral | None | None | None | None | N |
| E/Q | 0.3252 | likely_benign | 0.3266 | benign | -0.758 | Destabilizing | 0.999 | D | 0.695 | prob.neutral | N | 0.506456441 | None | None | N |
| E/R | 0.6706 | likely_pathogenic | 0.6514 | pathogenic | -0.447 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| E/S | 0.4333 | ambiguous | 0.4434 | ambiguous | -1.119 | Destabilizing | 0.997 | D | 0.651 | neutral | None | None | None | None | N |
| E/T | 0.5036 | ambiguous | 0.5026 | ambiguous | -0.889 | Destabilizing | 1.0 | D | 0.667 | neutral | None | None | None | None | N |
| E/V | 0.5009 | ambiguous | 0.5266 | ambiguous | -0.128 | Destabilizing | 1.0 | D | 0.659 | neutral | N | 0.472320291 | None | None | N |
| E/W | 0.9887 | likely_pathogenic | 0.9871 | pathogenic | -0.437 | Destabilizing | 1.0 | D | 0.717 | prob.delet. | None | None | None | None | N |
| E/Y | 0.926 | likely_pathogenic | 0.9194 | pathogenic | -0.343 | Destabilizing | 1.0 | D | 0.667 | 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.