Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 22797 | 68614;68615;68616 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| N2AB | 21156 | 63691;63692;63693 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| N2A | 20229 | 60910;60911;60912 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| N2B | 13732 | 41419;41420;41421 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| Novex-1 | 13857 | 41794;41795;41796 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| Novex-2 | 13924 | 41995;41996;41997 | chr2:178578126;178578125;178578124 | chr2:179442853;179442852;179442851 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/L | rs1371471381  |
-0.364 | 1.0 | N | 0.801 | 0.422 | 0.690650542524 | gnomAD-2.1.1 | 7.16E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.57E-05 | 0 |
| P/L | rs1371471381 |
-0.364 | 1.0 | N | 0.801 | 0.422 | 0.690650542524 | gnomAD-4.0.0 | 4.79122E-06 | None | None | None | None | N | None | 2.99204E-05 | 0 | None | 0 | 2.52347E-05 | None | 0 | 0 | 2.69914E-06 | 1.15985E-05 | 1.65717E-05 |
| P/Q | None | None | 0.985 | N | 0.398 | 0.367 | 0.502443086328 | gnomAD-4.0.0 | 1.36892E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 2.52347E-05 | None | 0 | 0 | 0 | 1.15985E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| P/A | 0.0933 | likely_benign | 0.0992 | benign | -1.151 | Destabilizing | 0.992 | D | 0.624 | neutral | N | 0.516209288 | None | None | N |
| P/C | 0.6189 | likely_pathogenic | 0.6516 | pathogenic | -0.61 | Destabilizing | 1.0 | D | 0.801 | deleterious | None | None | None | None | N |
| P/D | 0.8681 | likely_pathogenic | 0.9044 | pathogenic | -0.847 | Destabilizing | 0.998 | D | 0.713 | prob.delet. | None | None | None | None | N |
| P/E | 0.6523 | likely_pathogenic | 0.6897 | pathogenic | -0.903 | Destabilizing | 0.988 | D | 0.67 | neutral | None | None | None | None | N |
| P/F | 0.7508 | likely_pathogenic | 0.772 | pathogenic | -1.05 | Destabilizing | 1.0 | D | 0.825 | deleterious | None | None | None | None | N |
| P/G | 0.5647 | likely_pathogenic | 0.6223 | pathogenic | -1.404 | Destabilizing | 0.999 | D | 0.703 | prob.neutral | None | None | None | None | N |
| P/H | 0.5226 | ambiguous | 0.565 | pathogenic | -1.002 | Destabilizing | 1.0 | D | 0.793 | deleterious | None | None | None | None | N |
| P/I | 0.2857 | likely_benign | 0.2846 | benign | -0.582 | Destabilizing | 1.0 | D | 0.84 | deleterious | None | None | None | None | N |
| P/K | 0.7508 | likely_pathogenic | 0.7934 | pathogenic | -0.916 | Destabilizing | 0.996 | D | 0.705 | prob.neutral | None | None | None | None | N |
| P/L | 0.17 | likely_benign | 0.183 | benign | -0.582 | Destabilizing | 1.0 | D | 0.801 | deleterious | N | 0.466436615 | None | None | N |
| P/M | 0.3705 | ambiguous | 0.385 | ambiguous | -0.35 | Destabilizing | 1.0 | D | 0.791 | deleterious | None | None | None | None | N |
| P/N | 0.6163 | likely_pathogenic | 0.6806 | pathogenic | -0.56 | Destabilizing | 0.999 | D | 0.809 | deleterious | None | None | None | None | N |
| P/Q | 0.3759 | ambiguous | 0.3967 | ambiguous | -0.785 | Destabilizing | 0.985 | D | 0.398 | neutral | N | 0.476902193 | None | None | N |
| P/R | 0.5926 | likely_pathogenic | 0.6611 | pathogenic | -0.375 | Destabilizing | 0.999 | D | 0.813 | deleterious | N | 0.465186585 | None | None | N |
| P/S | 0.2494 | likely_benign | 0.2766 | benign | -1.015 | Destabilizing | 0.998 | D | 0.709 | prob.delet. | N | 0.491601632 | None | None | N |
| P/T | 0.1528 | likely_benign | 0.1729 | benign | -0.968 | Destabilizing | 0.999 | D | 0.746 | deleterious | N | 0.488852115 | None | None | N |
| P/V | 0.1845 | likely_benign | 0.19 | benign | -0.736 | Destabilizing | 0.999 | D | 0.792 | deleterious | None | None | None | None | N |
| P/W | 0.8931 | likely_pathogenic | 0.9147 | pathogenic | -1.193 | Destabilizing | 1.0 | D | 0.819 | deleterious | None | None | None | None | N |
| P/Y | 0.7517 | likely_pathogenic | 0.773 | pathogenic | -0.911 | Destabilizing | 1.0 | D | 0.826 | 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.