Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 23007 | 69244;69245;69246 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| N2AB | 21366 | 64321;64322;64323 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| N2A | 20439 | 61540;61541;61542 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| N2B | 13942 | 42049;42050;42051 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| Novex-1 | 14067 | 42424;42425;42426 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| Novex-2 | 14134 | 42625;42626;42627 | chr2:178577316;178577315;178577314 | chr2:179442043;179442042;179442041 |
| 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/T | rs1366649624  |
-2.786 | 0.124 | D | 0.702 | 0.732 | 0.78812575404 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | N | None | 0 | 2.9E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| I/T | rs1366649624 |
-2.786 | 0.124 | D | 0.702 | 0.732 | 0.78812575404 | gnomAD-4.0.0 | 1.5921E-06 | None | None | None | None | N | None | 0 | 2.28707E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| I/V | rs750858964 |
-1.597 | None | D | 0.276 | 0.327 | 0.321393169273 | gnomAD-2.1.1 | 8.05E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.78E-05 | 0 |
| I/V | rs750858964 |
-1.597 | None | D | 0.276 | 0.327 | 0.321393169273 | gnomAD-4.0.0 | 3.18417E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | 2.41313E-04 | 2.85971E-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 | 0.7449 | likely_pathogenic | 0.7481 | pathogenic | -2.573 | Highly Destabilizing | 0.072 | N | 0.697 | prob.neutral | None | None | None | None | N |
| I/C | 0.826 | likely_pathogenic | 0.8063 | pathogenic | -1.996 | Destabilizing | 0.909 | D | 0.771 | deleterious | None | None | None | None | N |
| I/D | 0.9705 | likely_pathogenic | 0.9694 | pathogenic | -2.767 | Highly Destabilizing | 0.726 | D | 0.839 | deleterious | None | None | None | None | N |
| I/E | 0.9088 | likely_pathogenic | 0.9073 | pathogenic | -2.601 | Highly Destabilizing | 0.726 | D | 0.831 | deleterious | None | None | None | None | N |
| I/F | 0.3891 | ambiguous | 0.3457 | ambiguous | -1.636 | Destabilizing | 0.497 | N | 0.734 | prob.delet. | D | 0.58131127 | None | None | N |
| I/G | 0.9275 | likely_pathogenic | 0.9276 | pathogenic | -3.078 | Highly Destabilizing | 0.726 | D | 0.808 | deleterious | None | None | None | None | N |
| I/H | 0.8578 | likely_pathogenic | 0.8279 | pathogenic | -2.43 | Highly Destabilizing | 0.968 | D | 0.825 | deleterious | None | None | None | None | N |
| I/K | 0.7789 | likely_pathogenic | 0.7252 | pathogenic | -1.979 | Destabilizing | 0.726 | D | 0.831 | deleterious | None | None | None | None | N |
| I/L | 0.1623 | likely_benign | 0.165 | benign | -1.138 | Destabilizing | 0.025 | N | 0.395 | neutral | D | 0.544156002 | None | None | N |
| I/M | 0.1703 | likely_benign | 0.1658 | benign | -1.066 | Destabilizing | 0.497 | N | 0.712 | prob.delet. | D | 0.616661018 | None | None | N |
| I/N | 0.685 | likely_pathogenic | 0.708 | pathogenic | -2.183 | Highly Destabilizing | 0.859 | D | 0.839 | deleterious | D | 0.618073648 | None | None | N |
| I/P | 0.9858 | likely_pathogenic | 0.9838 | pathogenic | -1.594 | Destabilizing | 0.726 | D | 0.844 | deleterious | None | None | None | None | N |
| I/Q | 0.8125 | likely_pathogenic | 0.7902 | pathogenic | -2.152 | Highly Destabilizing | 0.89 | D | 0.836 | deleterious | None | None | None | None | N |
| I/R | 0.7183 | likely_pathogenic | 0.669 | pathogenic | -1.55 | Destabilizing | 0.726 | D | 0.843 | deleterious | None | None | None | None | N |
| I/S | 0.7229 | likely_pathogenic | 0.7417 | pathogenic | -2.897 | Highly Destabilizing | 0.497 | N | 0.805 | deleterious | D | 0.611340873 | None | None | N |
| I/T | 0.6856 | likely_pathogenic | 0.675 | pathogenic | -2.591 | Highly Destabilizing | 0.124 | N | 0.702 | prob.neutral | D | 0.610937264 | None | None | N |
| I/V | 0.0727 | likely_benign | 0.0689 | benign | -1.594 | Destabilizing | None | N | 0.276 | neutral | D | 0.573157117 | None | None | N |
| I/W | 0.935 | likely_pathogenic | 0.915 | pathogenic | -1.955 | Destabilizing | 0.968 | D | 0.823 | deleterious | None | None | None | None | N |
| I/Y | 0.7599 | likely_pathogenic | 0.7642 | pathogenic | -1.702 | Destabilizing | 0.726 | D | 0.783 | 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.