Isoform Positions
| Isoform | Protein Position | Transcript Position | Chromosomal Position (HG38) | Chromosomal Position (HG19) |
|---|---|---|---|---|
| IC | 29297 | 88114;88115;88116 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| N2AB | 27656 | 83191;83192;83193 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| N2A | 26729 | 80410;80411;80412 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| N2B | 20232 | 60919;60920;60921 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| Novex-1 | 20357 | 61294;61295;61296 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| Novex-2 | 20424 | 61495;61496;61497 | chr2:178557373;178557372;178557371 | chr2:179422100;179422099;179422098 |
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/L | rs755953829  |
-1.207 | 0.011 | N | 0.217 | 0.24 | 0.28058544554 | gnomAD-2.1.1 | 8.04E-06 | None | None | None | None | I | None | 0 | 5.79E-05 | None | 0 | 0 | None | 0 | None | 0 | 0 | 0 |
| F/L | rs755953829 |
-1.207 | 0.011 | N | 0.217 | 0.24 | 0.28058544554 | gnomAD-4.0.0 | 3.18195E-06 | None | None | None | None | I | None | 0 | 4.57247E-05 | None | 0 | 0 | None | 0 | 0 | 0 | 0 | 0 |
| F/Y | rs373621460 |
-0.414 | 0.103 | N | 0.375 | 0.151 | None | gnomAD-2.1.1 | 4.02E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | None | 0 | 8.88E-06 | 0 |
| F/Y | rs373621460 |
-0.414 | 0.103 | N | 0.375 | 0.151 | None | gnomAD-4.0.0 | 1.59098E-06 | None | None | None | None | I | None | 0 | 0 | None | 0 | 0 | None | 0 | 0 | 2.85771E-06 | 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| F/A | 0.8157 | likely_pathogenic | 0.7812 | pathogenic | -2.47 | Highly Destabilizing | 0.919 | D | 0.553 | neutral | None | None | None | None | I |
| F/C | 0.3277 | likely_benign | 0.3397 | benign | -1.597 | Destabilizing | 0.999 | D | 0.7 | prob.neutral | N | 0.521983254 | None | None | I |
| F/D | 0.98 | likely_pathogenic | 0.9728 | pathogenic | -2.312 | Highly Destabilizing | 0.996 | D | 0.743 | deleterious | None | None | None | None | I |
| F/E | 0.9708 | likely_pathogenic | 0.9614 | pathogenic | -2.144 | Highly Destabilizing | 0.996 | D | 0.712 | prob.delet. | None | None | None | None | I |
| F/G | 0.9152 | likely_pathogenic | 0.905 | pathogenic | -2.873 | Highly Destabilizing | 0.996 | D | 0.664 | neutral | None | None | None | None | I |
| F/H | 0.6949 | likely_pathogenic | 0.6504 | pathogenic | -1.196 | Destabilizing | 0.988 | D | 0.595 | neutral | None | None | None | None | I |
| F/I | 0.5372 | ambiguous | 0.4652 | ambiguous | -1.193 | Destabilizing | 0.811 | D | 0.399 | neutral | N | 0.47820564 | None | None | I |
| F/K | 0.9618 | likely_pathogenic | 0.9553 | pathogenic | -2.006 | Highly Destabilizing | 0.988 | D | 0.705 | prob.neutral | None | None | None | None | I |
| F/L | 0.8543 | likely_pathogenic | 0.8363 | pathogenic | -1.193 | Destabilizing | 0.011 | N | 0.217 | neutral | N | 0.514246418 | None | None | I |
| F/M | 0.5668 | likely_pathogenic | 0.5355 | ambiguous | -0.872 | Destabilizing | 0.976 | D | 0.42 | neutral | None | None | None | None | I |
| F/N | 0.9128 | likely_pathogenic | 0.8936 | pathogenic | -2.38 | Highly Destabilizing | 0.996 | D | 0.754 | deleterious | None | None | None | None | I |
| F/P | 0.9988 | likely_pathogenic | 0.9988 | pathogenic | -1.622 | Destabilizing | 0.996 | D | 0.763 | deleterious | None | None | None | None | I |
| F/Q | 0.8836 | likely_pathogenic | 0.8666 | pathogenic | -2.346 | Highly Destabilizing | 0.996 | D | 0.761 | deleterious | None | None | None | None | I |
| F/R | 0.9126 | likely_pathogenic | 0.9005 | pathogenic | -1.442 | Destabilizing | 0.988 | D | 0.753 | deleterious | None | None | None | None | I |
| F/S | 0.7756 | likely_pathogenic | 0.7181 | pathogenic | -3.057 | Highly Destabilizing | 0.984 | D | 0.602 | neutral | D | 0.523430278 | None | None | I |
| F/T | 0.8435 | likely_pathogenic | 0.8053 | pathogenic | -2.782 | Highly Destabilizing | 0.988 | D | 0.606 | neutral | None | None | None | None | I |
| F/V | 0.4844 | ambiguous | 0.431 | ambiguous | -1.622 | Destabilizing | 0.811 | D | 0.483 | neutral | N | 0.463905911 | None | None | I |
| F/W | 0.597 | likely_pathogenic | 0.5783 | pathogenic | -0.276 | Destabilizing | 0.999 | D | 0.429 | neutral | None | None | None | None | I |
| F/Y | 0.1571 | likely_benign | 0.1435 | benign | -0.604 | Destabilizing | 0.103 | N | 0.375 | neutral | N | 0.449040146 | 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.