Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 16385 | 49378;49379;49380 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| N2AB | 14744 | 44455;44456;44457 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| N2A | 13817 | 41674;41675;41676 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| N2B | 7320 | 22183;22184;22185 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| Novex-1 | 7445 | 22558;22559;22560 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| Novex-2 | 7512 | 22759;22760;22761 | chr2:178614244;178614243;178614242 | chr2:179478971;179478970;179478969 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/D | None | None | 0.999 | N | 0.558 | 0.427 | 0.324986149311 | gnomAD-4.0.0 | 1.59351E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 3.03085E-05 |
| N/I | rs778033610  |
0.118 | 1.0 | D | 0.921 | 0.595 | 0.458917189328 | gnomAD-2.1.1 | 4.04E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.95E-06 | 0 |
| N/I | rs778033610 |
0.118 | 1.0 | D | 0.921 | 0.595 | 0.458917189328 | gnomAD-4.0.0 | 1.59352E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.86144E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| N/A | 0.8476 | likely_pathogenic | 0.7811 | pathogenic | -1.03 | Destabilizing | 1.0 | D | 0.818 | deleterious | None | None | None | None | N |
| N/C | 0.6323 | likely_pathogenic | 0.5218 | ambiguous | -0.459 | Destabilizing | 1.0 | D | 0.891 | deleterious | None | None | None | None | N |
| N/D | 0.8729 | likely_pathogenic | 0.7978 | pathogenic | -1.667 | Destabilizing | 0.999 | D | 0.558 | neutral | N | 0.497157478 | None | None | N |
| N/E | 0.9865 | likely_pathogenic | 0.9781 | pathogenic | -1.495 | Destabilizing | 0.999 | D | 0.607 | neutral | None | None | None | None | N |
| N/F | 0.9781 | likely_pathogenic | 0.9669 | pathogenic | -0.718 | Destabilizing | 1.0 | D | 0.925 | deleterious | None | None | None | None | N |
| N/G | 0.6893 | likely_pathogenic | 0.592 | pathogenic | -1.393 | Destabilizing | 0.999 | D | 0.527 | neutral | None | None | None | None | N |
| N/H | 0.4918 | ambiguous | 0.3737 | ambiguous | -0.999 | Destabilizing | 1.0 | D | 0.673 | neutral | N | 0.475241841 | None | None | N |
| N/I | 0.983 | likely_pathogenic | 0.9739 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.921 | deleterious | D | 0.577811933 | None | None | N |
| N/K | 0.9705 | likely_pathogenic | 0.9442 | pathogenic | -0.337 | Destabilizing | 1.0 | D | 0.643 | neutral | N | 0.473184277 | None | None | N |
| N/L | 0.9526 | likely_pathogenic | 0.9324 | pathogenic | -0.081 | Destabilizing | 1.0 | D | 0.895 | deleterious | None | None | None | None | N |
| N/M | 0.9719 | likely_pathogenic | 0.9543 | pathogenic | 0.275 | Stabilizing | 1.0 | D | 0.889 | deleterious | None | None | None | None | N |
| N/P | 0.9981 | likely_pathogenic | 0.997 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.914 | deleterious | None | None | None | None | N |
| N/Q | 0.9422 | likely_pathogenic | 0.9086 | pathogenic | -1.117 | Destabilizing | 1.0 | D | 0.697 | prob.neutral | None | None | None | None | N |
| N/R | 0.9186 | likely_pathogenic | 0.877 | pathogenic | -0.368 | Destabilizing | 1.0 | D | 0.665 | neutral | None | None | None | None | N |
| N/S | 0.2416 | likely_benign | 0.1851 | benign | -1.206 | Destabilizing | 0.999 | D | 0.53 | neutral | N | 0.477961315 | None | None | N |
| N/T | 0.8598 | likely_pathogenic | 0.7753 | pathogenic | -0.85 | Destabilizing | 0.999 | D | 0.59 | neutral | D | 0.533153029 | None | None | N |
| N/V | 0.965 | likely_pathogenic | 0.9476 | pathogenic | -0.369 | Destabilizing | 1.0 | D | 0.911 | deleterious | None | None | None | None | N |
| N/W | 0.9917 | likely_pathogenic | 0.9868 | pathogenic | -0.541 | Destabilizing | 1.0 | D | 0.853 | deleterious | None | None | None | None | N |
| N/Y | 0.8068 | likely_pathogenic | 0.7242 | pathogenic | -0.232 | Destabilizing | 1.0 | D | 0.91 | deleterious | N | 0.468385403 | 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.