Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 966 | 3121;3122;3123 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| N2AB | 966 | 3121;3122;3123 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| N2A | 966 | 3121;3122;3123 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| N2B | 920 | 2983;2984;2985 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| Novex-1 | 920 | 2983;2984;2985 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| Novex-2 | 920 | 2983;2984;2985 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
| Novex-3 | 966 | 3121;3122;3123 | chr2:178783010;178783009;178783008 | chr2:179647737;179647736;179647735 |
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/M | rs144408973  |
-1.016 | 0.998 | D | 0.73 | 0.458 | None | gnomAD-2.1.1 | 3.99E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.83E-06 | 0 |
| I/N | None | None | 0.999 | D | 0.814 | 0.696 | 0.911554315766 | gnomAD-4.0.0 | 2.40066E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.62502E-06 | 0 | 0 |
| I/V | rs2092911302 |
None | 0.333 | N | 0.213 | 0.175 | 0.369309618794 | gnomAD-4.0.0 | 3.1811E-06 | None | None | None | None | N | None | 0 | 2.28624E-05 | None | 0 | 0 | None | 0 | 0 | 2.85659E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| I/A | 0.982 | likely_pathogenic | 0.9898 | pathogenic | -2.658 | Highly Destabilizing | 0.992 | D | 0.685 | prob.neutral | None | None | None | None | N |
| I/C | 0.9891 | likely_pathogenic | 0.9938 | pathogenic | -2.043 | Highly Destabilizing | 1.0 | D | 0.736 | prob.delet. | None | None | None | None | N |
| I/D | 0.9996 | likely_pathogenic | 0.9998 | pathogenic | -2.672 | Highly Destabilizing | 1.0 | D | 0.831 | deleterious | None | None | None | None | N |
| I/E | 0.9988 | likely_pathogenic | 0.9994 | pathogenic | -2.436 | Highly Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| I/F | 0.7247 | likely_pathogenic | 0.8172 | pathogenic | -1.53 | Destabilizing | 0.998 | D | 0.761 | deleterious | D | 0.522102653 | None | None | N |
| I/G | 0.9984 | likely_pathogenic | 0.9992 | pathogenic | -3.216 | Highly Destabilizing | 1.0 | D | 0.823 | deleterious | None | None | None | None | N |
| I/H | 0.9973 | likely_pathogenic | 0.9988 | pathogenic | -2.555 | Highly Destabilizing | 1.0 | D | 0.786 | deleterious | None | None | None | None | N |
| I/K | 0.9968 | likely_pathogenic | 0.9983 | pathogenic | -1.93 | Destabilizing | 1.0 | D | 0.826 | deleterious | None | None | None | None | N |
| I/L | 0.3224 | likely_benign | 0.3925 | ambiguous | -1.036 | Destabilizing | 0.889 | D | 0.459 | neutral | N | 0.515106086 | None | None | N |
| I/M | 0.5666 | likely_pathogenic | 0.6688 | pathogenic | -1.13 | Destabilizing | 0.998 | D | 0.73 | prob.delet. | D | 0.555233971 | None | None | N |
| I/N | 0.9953 | likely_pathogenic | 0.9975 | pathogenic | -2.267 | Highly Destabilizing | 0.999 | D | 0.814 | deleterious | D | 0.612602828 | None | None | N |
| I/P | 0.9983 | likely_pathogenic | 0.9991 | pathogenic | -1.558 | Destabilizing | 1.0 | D | 0.815 | deleterious | None | None | None | None | N |
| I/Q | 0.9971 | likely_pathogenic | 0.9986 | pathogenic | -2.111 | Highly Destabilizing | 1.0 | D | 0.817 | deleterious | None | None | None | None | N |
| I/R | 0.9941 | likely_pathogenic | 0.9969 | pathogenic | -1.686 | Destabilizing | 1.0 | D | 0.822 | deleterious | None | None | None | None | N |
| I/S | 0.9906 | likely_pathogenic | 0.9952 | pathogenic | -3.04 | Highly Destabilizing | 0.998 | D | 0.81 | deleterious | N | 0.52013789 | None | None | N |
| I/T | 0.9807 | likely_pathogenic | 0.9886 | pathogenic | -2.652 | Highly Destabilizing | 0.989 | D | 0.759 | deleterious | N | 0.501628429 | None | None | N |
| I/V | 0.2098 | likely_benign | 0.2187 | benign | -1.558 | Destabilizing | 0.333 | N | 0.213 | neutral | N | 0.368033972 | None | None | N |
| I/W | 0.9966 | likely_pathogenic | 0.9984 | pathogenic | -1.837 | Destabilizing | 1.0 | D | 0.76 | deleterious | None | None | None | None | N |
| I/Y | 0.9815 | likely_pathogenic | 0.9906 | pathogenic | -1.592 | Destabilizing | 1.0 | D | 0.781 | deleterious | 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.