Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 19705 | 59338;59339;59340 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| N2AB | 18064 | 54415;54416;54417 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| N2A | 17137 | 51634;51635;51636 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| N2B | 10640 | 32143;32144;32145 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| Novex-1 | 10765 | 32518;32519;32520 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| Novex-2 | 10832 | 32719;32720;32721 | chr2:178593006;178593005;178593004 | chr2:179457733;179457732;179457731 |
| 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/C | rs72646839  |
-0.044 | 1.0 | N | 0.366 | 0.351 | None | gnomAD-2.1.1 | 2.25274E-04 | None | None | None | None | N | None | 1.24018E-04 | 4.24905E-04 | None | 3.87147E-04 | 0 | None | 0 | None | 0 | 3.05403E-04 | 2.81057E-04 |
| R/C | rs72646839 |
-0.044 | 1.0 | N | 0.366 | 0.351 | None | gnomAD-3.1.2 | 2.36873E-04 | None | None | None | None | N | None | 1.20814E-04 | 1.96799E-04 | 0 | 0 | 0 | None | 0 | 0 | 4.11874E-04 | 0 | 0 |
| R/C | rs72646839 |
-0.044 | 1.0 | N | 0.366 | 0.351 | None | gnomAD-4.0.0 | 2.14462E-04 | None | None | None | None | N | None | 9.33906E-05 | 4.0032E-04 | None | 3.04116E-04 | 0 | None | 1.5625E-05 | 0 | 2.46698E-04 | 0 | 2.24108E-04 |
| R/H | rs727503590 |
-0.591 | 0.999 | N | 0.416 | 0.333 | 0.398581233421 | gnomAD-2.1.1 | 2.15E-05 | None | None | None | None | N | None | 0 | 2.83E-05 | None | 0 | 0 | None | 3.27E-05 | None | 0 | 3.13E-05 | 0 |
| R/H | rs727503590 |
-0.591 | 0.999 | N | 0.416 | 0.333 | 0.398581233421 | gnomAD-3.1.2 | 3.29E-05 | None | None | None | None | N | None | 0 | 0 | 0 | 0 | 0 | None | 0 | 0 | 5.88E-05 | 2.07727E-04 | 0 |
| R/H | rs727503590 |
-0.591 | 0.999 | N | 0.416 | 0.333 | 0.398581233421 | gnomAD-4.0.0 | 1.6116E-05 | None | None | None | None | N | None | 0 | 3.33578E-05 | None | 0 | 0 | None | 0 | 0 | 1.94979E-05 | 1.09827E-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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| R/A | 0.6391 | likely_pathogenic | 0.5445 | ambiguous | 0.174 | Stabilizing | 0.863 | D | 0.401 | neutral | None | None | None | None | N |
| R/C | 0.3207 | likely_benign | 0.2291 | benign | 0.15 | Stabilizing | 1.0 | D | 0.366 | neutral | N | 0.4742953 | None | None | N |
| R/D | 0.8629 | likely_pathogenic | 0.8129 | pathogenic | -0.045 | Destabilizing | 0.969 | D | 0.458 | neutral | None | None | None | None | N |
| R/E | 0.5998 | likely_pathogenic | 0.5147 | ambiguous | 0.034 | Stabilizing | 0.939 | D | 0.4 | neutral | None | None | None | None | N |
| R/F | 0.6888 | likely_pathogenic | 0.6469 | pathogenic | 0.043 | Stabilizing | 0.997 | D | 0.393 | neutral | None | None | None | None | N |
| R/G | 0.5444 | ambiguous | 0.4271 | ambiguous | -0.045 | Destabilizing | 0.983 | D | 0.487 | neutral | N | 0.500895906 | None | None | N |
| R/H | 0.2097 | likely_benign | 0.1649 | benign | -0.709 | Destabilizing | 0.999 | D | 0.416 | neutral | N | 0.517769513 | None | None | N |
| R/I | 0.3792 | ambiguous | 0.3364 | benign | 0.723 | Stabilizing | 0.982 | D | 0.41 | neutral | None | None | None | None | N |
| R/K | 0.1769 | likely_benign | 0.1436 | benign | 0.162 | Stabilizing | 0.079 | N | 0.191 | neutral | None | None | None | None | N |
| R/L | 0.3588 | ambiguous | 0.3036 | benign | 0.723 | Stabilizing | 0.967 | D | 0.432 | neutral | N | 0.473170587 | None | None | N |
| R/M | 0.4701 | ambiguous | 0.3891 | ambiguous | 0.19 | Stabilizing | 0.997 | D | 0.405 | neutral | None | None | None | None | N |
| R/N | 0.8004 | likely_pathogenic | 0.7445 | pathogenic | 0.419 | Stabilizing | 0.969 | D | 0.419 | neutral | None | None | None | None | N |
| R/P | 0.7186 | likely_pathogenic | 0.6514 | pathogenic | 0.561 | Stabilizing | 0.998 | D | 0.422 | neutral | N | 0.481731355 | None | None | N |
| R/Q | 0.1888 | likely_benign | 0.149 | benign | 0.359 | Stabilizing | 0.939 | D | 0.448 | neutral | None | None | None | None | N |
| R/S | 0.748 | likely_pathogenic | 0.6641 | pathogenic | 0.154 | Stabilizing | 0.858 | D | 0.429 | neutral | N | 0.474458666 | None | None | N |
| R/T | 0.5268 | ambiguous | 0.4245 | ambiguous | 0.372 | Stabilizing | 0.079 | N | 0.211 | neutral | None | None | None | None | N |
| R/V | 0.4862 | ambiguous | 0.4279 | ambiguous | 0.561 | Stabilizing | 0.939 | D | 0.463 | neutral | None | None | None | None | N |
| R/W | 0.2956 | likely_benign | 0.2324 | benign | -0.037 | Destabilizing | 0.999 | D | 0.401 | neutral | None | None | None | None | N |
| R/Y | 0.5311 | ambiguous | 0.4689 | ambiguous | 0.37 | Stabilizing | 0.997 | D | 0.419 | neutral | 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.