Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 25783 | 77572;77573;77574 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| N2AB | 24142 | 72649;72650;72651 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| N2A | 23215 | 69868;69869;69870 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| N2B | 16718 | 50377;50378;50379 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| Novex-1 | 16843 | 50752;50753;50754 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| Novex-2 | 16910 | 50953;50954;50955 | chr2:178568785;178568784;178568783 | chr2:179433512;179433511;179433510 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/Q | rs777428147  |
-0.448 | 1.0 | N | 0.585 | 0.263 | 0.203808441222 | gnomAD-2.1.1 | 6.1E-05 | None | None | None | None | I | None | 4.14E-05 | 1.13449E-04 | None | 0 | 1.03157E-04 | None | 1.3113E-04 | None | 0 | 3.94E-05 | 1.41483E-04 |
| R/Q | rs777428147 |
-0.448 | 1.0 | N | 0.585 | 0.263 | 0.203808441222 | gnomAD-3.1.2 | 4.6E-05 | None | None | None | None | I | None | 4.83E-05 | 0 | 0 | 0 | 1.93573E-04 | None | 0 | 0 | 2.94E-05 | 0 | 9.56938E-04 |
| R/Q | rs777428147 |
-0.448 | 1.0 | N | 0.585 | 0.263 | 0.203808441222 | gnomAD-4.0.0 | 4.09253E-05 | None | None | None | None | I | None | 4.0078E-05 | 6.67534E-05 | None | 0 | 6.70391E-05 | None | 0 | 0 | 3.98538E-05 | 5.49571E-05 | 6.40861E-05 |
| R/W | rs758010128 |
-0.295 | 1.0 | N | 0.674 | 0.4 | 0.276482976112 | gnomAD-2.1.1 | 1.21E-05 | None | None | None | None | I | None | 0 | 8.72E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| R/W | rs758010128 |
-0.295 | 1.0 | N | 0.674 | 0.4 | 0.276482976112 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 1.47E-05 | 0 | 0 |
| R/W | rs758010128 |
-0.295 | 1.0 | N | 0.674 | 0.4 | 0.276482976112 | gnomAD-4.0.0 | 6.20017E-06 | None | None | None | None | I | None | 0 | 5.00634E-05 | None | 0 | 0 | None | 0 | 0 | 4.23935E-06 | 1.09895E-05 | 1.60215E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6978 | likely_pathogenic | 0.7381 | pathogenic | -1.017 | Destabilizing | 0.96 | D | 0.547 | neutral | None | None | None | None | I |
| R/C | 0.2751 | likely_benign | 0.318 | benign | -0.947 | Destabilizing | 1.0 | D | 0.711 | prob.delet. | None | None | None | None | I |
| R/D | 0.9661 | likely_pathogenic | 0.9708 | pathogenic | -0.092 | Destabilizing | 0.999 | D | 0.709 | prob.delet. | None | None | None | None | I |
| R/E | 0.8075 | likely_pathogenic | 0.8339 | pathogenic | 0.064 | Stabilizing | 0.967 | D | 0.499 | neutral | None | None | None | None | I |
| R/F | 0.8749 | likely_pathogenic | 0.8978 | pathogenic | -0.642 | Destabilizing | 0.985 | D | 0.722 | prob.delet. | None | None | None | None | I |
| R/G | 0.7175 | likely_pathogenic | 0.7528 | pathogenic | -1.365 | Destabilizing | 0.995 | D | 0.609 | neutral | N | 0.483286006 | None | None | I |
| R/H | 0.307 | likely_benign | 0.3486 | ambiguous | -1.585 | Destabilizing | 0.999 | D | 0.614 | neutral | None | None | None | None | I |
| R/I | 0.572 | likely_pathogenic | 0.612 | pathogenic | -0.063 | Destabilizing | 0.908 | D | 0.629 | neutral | None | None | None | None | I |
| R/K | 0.2341 | likely_benign | 0.2563 | benign | -0.962 | Destabilizing | 0.826 | D | 0.485 | neutral | None | None | None | None | I |
| R/L | 0.6315 | likely_pathogenic | 0.6654 | pathogenic | -0.063 | Destabilizing | 0.95 | D | 0.571 | neutral | N | 0.474127805 | None | None | I |
| R/M | 0.6602 | likely_pathogenic | 0.7111 | pathogenic | -0.461 | Destabilizing | 0.993 | D | 0.703 | prob.neutral | None | None | None | None | I |
| R/N | 0.9181 | likely_pathogenic | 0.9282 | pathogenic | -0.488 | Destabilizing | 0.999 | D | 0.567 | neutral | None | None | None | None | I |
| R/P | 0.9761 | likely_pathogenic | 0.978 | pathogenic | -0.361 | Destabilizing | 0.999 | D | 0.704 | prob.neutral | N | 0.477072642 | None | None | I |
| R/Q | 0.2103 | likely_benign | 0.2359 | benign | -0.575 | Destabilizing | 1.0 | D | 0.585 | neutral | N | 0.488340042 | None | None | I |
| R/S | 0.8173 | likely_pathogenic | 0.8437 | pathogenic | -1.32 | Destabilizing | 0.997 | D | 0.617 | neutral | None | None | None | None | I |
| R/T | 0.6194 | likely_pathogenic | 0.6693 | pathogenic | -0.963 | Destabilizing | 0.979 | D | 0.592 | neutral | None | None | None | None | I |
| R/V | 0.5658 | likely_pathogenic | 0.6072 | pathogenic | -0.361 | Destabilizing | 0.043 | N | 0.564 | neutral | None | None | None | None | I |
| R/W | 0.6034 | likely_pathogenic | 0.6486 | pathogenic | -0.222 | Destabilizing | 1.0 | D | 0.674 | neutral | N | 0.48910051 | None | None | I |
| R/Y | 0.7624 | likely_pathogenic | 0.7935 | pathogenic | 0.022 | Stabilizing | 0.993 | D | 0.714 | prob.delet. | None | None | None | None | I |
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.