Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 30261 | 91006;91007;91008 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| N2AB | 28620 | 86083;86084;86085 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| N2A | 27693 | 83302;83303;83304 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| N2B | 21196 | 63811;63812;63813 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| Novex-1 | 21321 | 64186;64187;64188 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| Novex-2 | 21388 | 64387;64388;64389 | chr2:178552119;178552118;178552117 | chr2:179416846;179416845;179416844 |
| 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/G | None | None | 0.994 | N | 0.547 | 0.275 | 0.300784259202 | gnomAD-4.0.0 | 3.18256E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 5.71651E-06 | 0 | 0 |
| S/I | None | None | 0.998 | N | 0.658 | 0.365 | 0.384919354899 | gnomAD-4.0.0 | 6.84236E-07 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 8.99488E-07 | 0 | 0 |
| S/T | None | None | 0.994 | N | 0.545 | 0.238 | 0.227260227426 | gnomAD-4.0.0 | 2.05271E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 3.47923E-05 | 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 | 0.152 | likely_benign | 0.1311 | benign | -0.748 | Destabilizing | 0.98 | D | 0.477 | neutral | None | None | None | None | I |
| S/C | 0.1748 | likely_benign | 0.1472 | benign | -0.874 | Destabilizing | 0.391 | N | 0.478 | neutral | N | 0.493663289 | None | None | I |
| S/D | 0.9316 | likely_pathogenic | 0.9032 | pathogenic | -2.089 | Highly Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| S/E | 0.943 | likely_pathogenic | 0.9192 | pathogenic | -1.895 | Destabilizing | 1.0 | D | 0.64 | neutral | None | None | None | None | I |
| S/F | 0.6476 | likely_pathogenic | 0.5206 | ambiguous | -0.576 | Destabilizing | 1.0 | D | 0.705 | prob.neutral | None | None | None | None | I |
| S/G | 0.3215 | likely_benign | 0.2806 | benign | -1.123 | Destabilizing | 0.994 | D | 0.547 | neutral | N | 0.512171692 | None | None | I |
| S/H | 0.8073 | likely_pathogenic | 0.7184 | pathogenic | -1.569 | Destabilizing | 1.0 | D | 0.677 | prob.neutral | None | None | None | None | I |
| S/I | 0.315 | likely_benign | 0.2504 | benign | 0.196 | Stabilizing | 0.998 | D | 0.658 | neutral | N | 0.330546468 | None | None | I |
| S/K | 0.9877 | likely_pathogenic | 0.9757 | pathogenic | -0.589 | Destabilizing | 1.0 | D | 0.62 | neutral | None | None | None | None | I |
| S/L | 0.2732 | likely_benign | 0.2007 | benign | 0.196 | Stabilizing | 0.992 | D | 0.569 | neutral | None | None | None | None | I |
| S/M | 0.4186 | ambiguous | 0.3251 | benign | 0.045 | Stabilizing | 1.0 | D | 0.675 | prob.neutral | None | None | None | None | I |
| S/N | 0.5051 | ambiguous | 0.4269 | ambiguous | -1.41 | Destabilizing | 0.999 | D | 0.634 | neutral | N | 0.458259849 | None | None | I |
| S/P | 0.9887 | likely_pathogenic | 0.9876 | pathogenic | -0.085 | Destabilizing | 1.0 | D | 0.662 | neutral | None | None | None | None | I |
| S/Q | 0.892 | likely_pathogenic | 0.8491 | pathogenic | -1.125 | Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | I |
| S/R | 0.9724 | likely_pathogenic | 0.9501 | pathogenic | -0.951 | Destabilizing | 0.999 | D | 0.661 | neutral | N | 0.45246724 | None | None | I |
| S/T | 0.1398 | likely_benign | 0.1121 | benign | -0.942 | Destabilizing | 0.994 | D | 0.545 | neutral | N | 0.394421801 | None | None | I |
| S/V | 0.3205 | likely_benign | 0.2581 | benign | -0.085 | Destabilizing | 0.998 | D | 0.622 | neutral | None | None | None | None | I |
| S/W | 0.7818 | likely_pathogenic | 0.717 | pathogenic | -0.983 | Destabilizing | 1.0 | D | 0.707 | prob.neutral | None | None | None | None | I |
| S/Y | 0.585 | likely_pathogenic | 0.4846 | ambiguous | -0.5 | Destabilizing | 1.0 | D | 0.703 | prob.neutral | None | None | None | None | I |
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.