Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 6954 | 21085;21086;21087 | chr2:178724515;178724514;178724513 | chr2:179589242;179589241;179589240 |
| N2AB | 6637 | 20134;20135;20136 | chr2:178724515;178724514;178724513 | chr2:179589242;179589241;179589240 |
| N2A | 5710 | 17353;17354;17355 | chr2:178724515;178724514;178724513 | chr2:179589242;179589241;179589240 |
| N2B | None | None | chr2:None | chr2:None |
| Novex-1 | None | None | chr2:None | chr2:None |
| Novex-2 | None | None | chr2:None | chr2:None |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/V | rs17355446  |
-0.508 | 0.811 | N | 0.435 | 0.2 | None | gnomAD-2.1.1 | 5.29469E-02 | None | None | None | None | I | None | 6.34802E-03 | 1.83134E-01 | None | 1.88031E-02 | 7.2232E-04 | None | 1.27993E-01 | None | 5.50012E-02 | 1.93188E-02 | 4.53893E-02 |
| A/V | rs17355446 |
-0.508 | 0.811 | N | 0.435 | 0.2 | None | gnomAD-3.1.2 | 3.25654E-02 | None | None | None | None | I | None | 6.59197E-03 | 1.30266E-01 | 4.27632E-02 | 1.70127E-02 | 1.55039E-03 | None | 5.66767E-02 | 2.21519E-02 | 1.94016E-02 | 1.24325E-01 | 2.87356E-02 |
| A/V | rs17355446 |
-0.508 | 0.811 | N | 0.435 | 0.2 | None | 1000 genomes | 5.15176E-02 | None | None | None | None | I | None | 2.3E-03 | 1.441E-01 | None | None | 2E-03 | 2.98E-02 | None | None | None | 1.258E-01 | None |
| A/V | rs17355446 |
-0.508 | 0.811 | N | 0.435 | 0.2 | None | gnomAD-4.0.0 | 3.16713E-02 | None | None | None | None | I | None | 5.91422E-03 | 1.67067E-01 | None | 1.90398E-02 | 6.28874E-04 | None | 5.66263E-02 | 3.62513E-02 | 1.97014E-02 | 1.20922E-01 | 3.19321E-02 |
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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| A/C | 0.7386 | likely_pathogenic | 0.6417 | pathogenic | -0.737 | Destabilizing | 0.999 | D | 0.517 | neutral | None | None | None | None | I |
| A/D | 0.7831 | likely_pathogenic | 0.6321 | pathogenic | -0.778 | Destabilizing | 0.976 | D | 0.565 | neutral | None | None | None | None | I |
| A/E | 0.7297 | likely_pathogenic | 0.5867 | pathogenic | -0.857 | Destabilizing | 0.968 | D | 0.56 | neutral | N | 0.434217049 | None | None | I |
| A/F | 0.7659 | likely_pathogenic | 0.647 | pathogenic | -0.975 | Destabilizing | 0.988 | D | 0.619 | neutral | None | None | None | None | I |
| A/G | 0.262 | likely_benign | 0.2054 | benign | -0.881 | Destabilizing | 0.896 | D | 0.455 | neutral | N | 0.455669756 | None | None | I |
| A/H | 0.9104 | likely_pathogenic | 0.8357 | pathogenic | -1.13 | Destabilizing | 0.999 | D | 0.598 | neutral | None | None | None | None | I |
| A/I | 0.4563 | ambiguous | 0.3504 | ambiguous | -0.316 | Destabilizing | 0.261 | N | 0.403 | neutral | None | None | None | None | I |
| A/K | 0.9209 | likely_pathogenic | 0.8479 | pathogenic | -1.021 | Destabilizing | 0.976 | D | 0.56 | neutral | None | None | None | None | I |
| A/L | 0.3457 | ambiguous | 0.2853 | benign | -0.316 | Destabilizing | 0.851 | D | 0.469 | neutral | None | None | None | None | I |
| A/M | 0.4712 | ambiguous | 0.3605 | ambiguous | -0.266 | Destabilizing | 0.997 | D | 0.575 | neutral | None | None | None | None | I |
| A/N | 0.727 | likely_pathogenic | 0.5567 | ambiguous | -0.618 | Destabilizing | 0.976 | D | 0.593 | neutral | None | None | None | None | I |
| A/P | 0.1576 | likely_benign | 0.1397 | benign | -0.397 | Destabilizing | 0.059 | N | 0.292 | neutral | N | 0.352230383 | None | None | I |
| A/Q | 0.8132 | likely_pathogenic | 0.7115 | pathogenic | -0.813 | Destabilizing | 0.988 | D | 0.604 | neutral | None | None | None | None | I |
| A/R | 0.8718 | likely_pathogenic | 0.801 | pathogenic | -0.681 | Destabilizing | 0.988 | D | 0.607 | neutral | None | None | None | None | I |
| A/S | 0.2136 | likely_benign | 0.1628 | benign | -0.914 | Destabilizing | 0.251 | N | 0.274 | neutral | N | 0.405318294 | None | None | I |
| A/T | 0.1776 | likely_benign | 0.1281 | benign | -0.901 | Destabilizing | 0.103 | N | 0.281 | neutral | N | 0.420671748 | None | None | I |
| A/V | 0.1995 | likely_benign | 0.1557 | benign | -0.397 | Destabilizing | 0.811 | D | 0.435 | neutral | N | 0.468540266 | None | None | I |
| A/W | 0.9538 | likely_pathogenic | 0.9151 | pathogenic | -1.257 | Destabilizing | 0.999 | D | 0.656 | neutral | None | None | None | None | I |
| A/Y | 0.8717 | likely_pathogenic | 0.7739 | pathogenic | -0.869 | Destabilizing | 0.996 | D | 0.629 | 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.