Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25637 | 77134;77135;77136 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| N2AB | 23996 | 72211;72212;72213 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| N2A | 23069 | 69430;69431;69432 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| N2B | 16572 | 49939;49940;49941 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| Novex-1 | 16697 | 50314;50315;50316 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| Novex-2 | 16764 | 50515;50516;50517 | chr2:178569223;178569222;178569221 | chr2:179433950;179433949;179433948 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/V | rs1282968520  |
-1.834 | 0.011 | N | 0.265 | 0.076 | 0.427713192076 | gnomAD-2.1.1 | 8.26E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 5.61E-05 | None | 3.47E-05 | None | 0 | 0 | 0 |
| I/V | rs1282968520 |
-1.834 | 0.011 | N | 0.265 | 0.076 | 0.427713192076 | gnomAD-3.1.2 | 6.57E-06 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 1.93498E-04 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs1282968520 |
-1.834 | 0.011 | N | 0.265 | 0.076 | 0.427713192076 | gnomAD-4.0.0 | 3.73926E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.23424E-05 | None | 0 | 0 | 2.5535E-06 | 1.11527E-05 | 1.61337E-05 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.6778 | likely_pathogenic | 0.7102 | pathogenic | -2.557 | Highly Destabilizing | 0.993 | D | 0.545 | neutral | None | None | None | None | N |
| I/C | 0.8241 | likely_pathogenic | 0.8349 | pathogenic | -2.04 | Highly Destabilizing | 1.0 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/D | 0.9816 | likely_pathogenic | 0.9823 | pathogenic | -3.144 | Highly Destabilizing | 1.0 | D | 0.725 | prob.delet. | None | None | None | None | N |
| I/E | 0.9433 | likely_pathogenic | 0.943 | pathogenic | -3.015 | Highly Destabilizing | 0.999 | D | 0.702 | prob.neutral | None | None | None | None | N |
| I/F | 0.3821 | ambiguous | 0.417 | ambiguous | -1.588 | Destabilizing | 0.998 | D | 0.656 | neutral | N | 0.481800037 | None | None | N |
| I/G | 0.9559 | likely_pathogenic | 0.9596 | pathogenic | -2.995 | Highly Destabilizing | 0.999 | D | 0.689 | prob.neutral | None | None | None | None | N |
| I/H | 0.7539 | likely_pathogenic | 0.7561 | pathogenic | -2.257 | Highly Destabilizing | 1.0 | D | 0.715 | prob.delet. | None | None | None | None | N |
| I/K | 0.7821 | likely_pathogenic | 0.7793 | pathogenic | -1.989 | Destabilizing | 0.983 | D | 0.709 | prob.delet. | None | None | None | None | N |
| I/L | 0.231 | likely_benign | 0.2444 | benign | -1.323 | Destabilizing | 0.359 | N | 0.411 | neutral | N | 0.501413194 | None | None | N |
| I/M | 0.221 | likely_benign | 0.2315 | benign | -1.313 | Destabilizing | 0.994 | D | 0.673 | neutral | N | 0.510375225 | None | None | N |
| I/N | 0.7676 | likely_pathogenic | 0.7698 | pathogenic | -2.177 | Highly Destabilizing | 1.0 | D | 0.74 | deleterious | N | 0.487596481 | None | None | N |
| I/P | 0.9949 | likely_pathogenic | 0.9952 | pathogenic | -1.714 | Destabilizing | 1.0 | D | 0.734 | prob.delet. | None | None | None | None | N |
| I/Q | 0.8239 | likely_pathogenic | 0.821 | pathogenic | -2.223 | Highly Destabilizing | 1.0 | D | 0.733 | prob.delet. | None | None | None | None | N |
| I/R | 0.6497 | likely_pathogenic | 0.6418 | pathogenic | -1.454 | Destabilizing | 1.0 | D | 0.739 | prob.delet. | None | None | None | None | N |
| I/S | 0.7001 | likely_pathogenic | 0.7148 | pathogenic | -2.773 | Highly Destabilizing | 0.999 | D | 0.638 | neutral | N | 0.474149807 | None | None | N |
| I/T | 0.3415 | ambiguous | 0.3633 | ambiguous | -2.526 | Highly Destabilizing | 0.984 | D | 0.599 | neutral | N | 0.471960988 | None | None | N |
| I/V | 0.0739 | likely_benign | 0.0801 | benign | -1.714 | Destabilizing | 0.011 | N | 0.265 | neutral | N | 0.467281977 | None | None | N |
| I/W | 0.9133 | likely_pathogenic | 0.9195 | pathogenic | -1.89 | Destabilizing | 1.0 | D | 0.678 | prob.neutral | None | None | None | None | N |
| I/Y | 0.7865 | likely_pathogenic | 0.7938 | pathogenic | -1.682 | Destabilizing | 0.996 | D | 0.679 | prob.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.