Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 24238 | 72937;72938;72939 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| N2AB | 22597 | 68014;68015;68016 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| N2A | 21670 | 65233;65234;65235 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| N2B | 15173 | 45742;45743;45744 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| Novex-1 | 15298 | 46117;46118;46119 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| Novex-2 | 15365 | 46318;46319;46320 | chr2:178573420;178573419;178573418 | chr2:179438147;179438146;179438145 |
| 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/L | rs786205303  |
0.008 | 0.959 | D | 0.675 | 0.404 | 0.714212821129 | gnomAD-2.1.1 | 9.64E-06 | None | None | None | None | N | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 1.97E-05 | 0 |
| S/L | rs786205303 |
0.008 | 0.959 | D | 0.675 | 0.404 | 0.714212821129 | gnomAD-3.1.2 | 1.32E-05 | None | None | None | None | N | None | 2.42E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| S/L | rs786205303 |
0.008 | 0.959 | D | 0.675 | 0.404 | 0.714212821129 | gnomAD-4.0.0 | 4.41065E-05 | None | None | None | None | N | None | 2.78995E-05 | 0 | None | 0 | 0 | None | 0 | 1.77117E-04 | 5.27979E-05 | 0 | 6.84861E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| S/A | 0.1318 | likely_benign | 0.1304 | benign | -0.488 | Destabilizing | 0.025 | N | 0.217 | neutral | N | 0.47729163 | None | None | N |
| S/C | 0.126 | likely_benign | 0.1248 | benign | -0.929 | Destabilizing | 0.997 | D | 0.756 | deleterious | None | None | None | None | N |
| S/D | 0.8643 | likely_pathogenic | 0.8527 | pathogenic | -2.043 | Highly Destabilizing | 0.957 | D | 0.555 | neutral | None | None | None | None | N |
| S/E | 0.8791 | likely_pathogenic | 0.8803 | pathogenic | -1.97 | Destabilizing | 0.916 | D | 0.534 | neutral | None | None | None | None | N |
| S/F | 0.3025 | likely_benign | 0.2709 | benign | -0.815 | Destabilizing | 0.987 | D | 0.827 | deleterious | None | None | None | None | N |
| S/G | 0.1635 | likely_benign | 0.17 | benign | -0.743 | Destabilizing | 0.845 | D | 0.448 | neutral | None | None | None | None | N |
| S/H | 0.5565 | ambiguous | 0.559 | ambiguous | -1.28 | Destabilizing | 0.999 | D | 0.759 | deleterious | None | None | None | None | N |
| S/I | 0.5444 | ambiguous | 0.5036 | ambiguous | 0.094 | Stabilizing | 0.975 | D | 0.811 | deleterious | None | None | None | None | N |
| S/K | 0.9515 | likely_pathogenic | 0.9522 | pathogenic | -0.687 | Destabilizing | 0.916 | D | 0.531 | neutral | None | None | None | None | N |
| S/L | 0.2181 | likely_benign | 0.2072 | benign | 0.094 | Stabilizing | 0.959 | D | 0.675 | prob.neutral | D | 0.542266365 | None | None | N |
| S/M | 0.2873 | likely_benign | 0.2811 | benign | 0.22 | Stabilizing | 0.999 | D | 0.761 | deleterious | None | None | None | None | N |
| S/N | 0.3601 | ambiguous | 0.3469 | ambiguous | -1.25 | Destabilizing | 0.987 | D | 0.583 | neutral | None | None | None | None | N |
| S/P | 0.9947 | likely_pathogenic | 0.9926 | pathogenic | -0.068 | Destabilizing | 0.983 | D | 0.767 | deleterious | D | 0.542266365 | None | None | N |
| S/Q | 0.7845 | likely_pathogenic | 0.7869 | pathogenic | -1.372 | Destabilizing | 0.987 | D | 0.658 | neutral | None | None | None | None | N |
| S/R | 0.9217 | likely_pathogenic | 0.9239 | pathogenic | -0.618 | Destabilizing | 0.987 | D | 0.777 | deleterious | None | None | None | None | N |
| S/T | 0.1156 | likely_benign | 0.118 | benign | -0.902 | Destabilizing | 0.892 | D | 0.447 | neutral | N | 0.472946309 | None | None | N |
| S/V | 0.4701 | ambiguous | 0.4421 | ambiguous | -0.068 | Destabilizing | 0.95 | D | 0.731 | prob.delet. | None | None | None | None | N |
| S/W | 0.653 | likely_pathogenic | 0.6174 | pathogenic | -1.033 | Destabilizing | 0.999 | D | 0.774 | deleterious | N | 0.51938917 | None | None | N |
| S/Y | 0.3222 | likely_benign | 0.3103 | benign | -0.582 | Destabilizing | 0.996 | D | 0.822 | 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.