Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 27494 | 82705;82706;82707 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| N2AB | 25853 | 77782;77783;77784 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| N2A | 24926 | 75001;75002;75003 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| N2B | 18429 | 55510;55511;55512 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| Novex-1 | 18554 | 55885;55886;55887 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| Novex-2 | 18621 | 56086;56087;56088 | chr2:178563652;178563651;178563650 | chr2:179428379;179428378;179428377 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | rs563168332  |
-0.027 | 0.005 | N | 0.126 | 0.058 | 0.21737058555 | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 6.46E-05 | 0 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| V/A | rs563168332 |
-0.027 | 0.005 | N | 0.126 | 0.058 | 0.21737058555 | gnomAD-3.1.2 | 6.58E-06 | None | None | None | None | I | None | 2.41E-05 | 0 | 0 | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| V/A | rs563168332 |
-0.027 | 0.005 | N | 0.126 | 0.058 | 0.21737058555 | 1000 genomes | 1.99681E-04 | None | None | None | None | I | None | 8E-04 | 0 | None | None | 0 | 0 | None | None | None | 0 | None |
| V/A | rs563168332 |
-0.027 | 0.005 | N | 0.126 | 0.058 | 0.21737058555 | gnomAD-4.0.0 | 6.57022E-06 | None | None | None | None | I | None | 2.40697E-05 | 0 | None | 0 | 0 | None | 0 | 0 | 0 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| V/A | 0.0702 | likely_benign | 0.0751 | benign | -0.243 | Destabilizing | 0.005 | N | 0.126 | neutral | N | 0.372331589 | None | None | I |
| V/C | 0.5063 | ambiguous | 0.5198 | ambiguous | -0.578 | Destabilizing | 0.864 | D | 0.249 | neutral | None | None | None | None | I |
| V/D | 0.1383 | likely_benign | 0.1461 | benign | -0.407 | Destabilizing | None | N | 0.146 | neutral | None | None | None | None | I |
| V/E | 0.111 | likely_benign | 0.1134 | benign | -0.541 | Destabilizing | None | N | 0.115 | neutral | N | 0.362114595 | None | None | I |
| V/F | 0.1456 | likely_benign | 0.1531 | benign | -0.711 | Destabilizing | 0.214 | N | 0.329 | neutral | None | None | None | None | I |
| V/G | 0.1 | likely_benign | 0.096 | benign | -0.301 | Destabilizing | 0.024 | N | 0.311 | neutral | N | 0.433593478 | None | None | I |
| V/H | 0.3059 | likely_benign | 0.312 | benign | 0.009 | Stabilizing | 0.356 | N | 0.305 | neutral | None | None | None | None | I |
| V/I | 0.0729 | likely_benign | 0.0764 | benign | -0.244 | Destabilizing | None | N | 0.081 | neutral | N | 0.425859429 | None | None | I |
| V/K | 0.1366 | likely_benign | 0.135 | benign | -0.283 | Destabilizing | None | N | 0.128 | neutral | None | None | None | None | I |
| V/L | 0.1021 | likely_benign | 0.1054 | benign | -0.244 | Destabilizing | 0.002 | N | 0.122 | neutral | N | 0.426166073 | None | None | I |
| V/M | 0.0921 | likely_benign | 0.0949 | benign | -0.389 | Destabilizing | 0.214 | N | 0.235 | neutral | None | None | None | None | I |
| V/N | 0.1199 | likely_benign | 0.1303 | benign | None | Stabilizing | 0.072 | N | 0.387 | neutral | None | None | None | None | I |
| V/P | 0.1999 | likely_benign | 0.2116 | benign | -0.214 | Destabilizing | 0.136 | N | 0.399 | neutral | None | None | None | None | I |
| V/Q | 0.1455 | likely_benign | 0.1461 | benign | -0.26 | Destabilizing | 0.001 | N | 0.162 | neutral | None | None | None | None | I |
| V/R | 0.1437 | likely_benign | 0.1416 | benign | 0.19 | Stabilizing | 0.038 | N | 0.389 | neutral | None | None | None | None | I |
| V/S | 0.0903 | likely_benign | 0.0962 | benign | -0.268 | Destabilizing | 0.031 | N | 0.246 | neutral | None | None | None | None | I |
| V/T | 0.0826 | likely_benign | 0.0885 | benign | -0.314 | Destabilizing | 0.031 | N | 0.189 | neutral | None | None | None | None | I |
| V/W | 0.6051 | likely_pathogenic | 0.6072 | pathogenic | -0.781 | Destabilizing | 0.864 | D | 0.263 | neutral | None | None | None | None | I |
| V/Y | 0.3665 | ambiguous | 0.377 | ambiguous | -0.478 | Destabilizing | 0.356 | N | 0.329 | neutral | 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.