TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29430	88513;88514;88515	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
N2AB	27789	83590;83591;83592	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
N2A	26862	80809;80810;80811	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
N2B	20365	61318;61319;61320	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
Novex-1	20490	61693;61694;61695	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
Novex-2	20557	61894;61895;61896	chr2:178556866;178556865;178556864	chr2:179421593;179421592;179421591
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-102
• Domain position: 96
• Structural Position: 129
• Q(SASA): 0.3246
• Predicted PPI site: N

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
T/I	rs1224484023	0.082	0.999	N	0.769	0.402	0.409398589964	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/P	None	None	0.999	N	0.759	0.395	0.405012372841	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
T/A	0.1063	likely_benign	0.0918	benign	-0.774	Destabilizing	0.997	D	0.763	deleterious	N	0.513264983	None	None	N
T/C	0.4466	ambiguous	0.4031	ambiguous	-0.546	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
T/D	0.5741	likely_pathogenic	0.4768	ambiguous	-0.082	Destabilizing	0.999	D	0.776	deleterious	None	None	None	None	N
T/E	0.4291	ambiguous	0.3556	ambiguous	-0.079	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
T/F	0.3315	likely_benign	0.2592	benign	-0.861	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
T/G	0.4316	ambiguous	0.3618	ambiguous	-1.029	Destabilizing	0.999	D	0.663	prob.neutral	None	None	None	None	N
T/H	0.3156	likely_benign	0.2593	benign	-1.272	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/I	0.1466	likely_benign	0.1212	benign	-0.19	Destabilizing	0.999	D	0.769	deleterious	N	0.460027931	None	None	N
T/K	0.2507	likely_benign	0.1999	benign	-0.688	Destabilizing	0.999	D	0.779	deleterious	None	None	None	None	N
T/L	0.1094	likely_benign	0.0944	benign	-0.19	Destabilizing	0.998	D	0.762	deleterious	None	None	None	None	N
T/M	0.1039	likely_benign	0.0971	benign	0.009	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/N	0.1722	likely_benign	0.1457	benign	-0.659	Destabilizing	0.999	D	0.729	deleterious	N	0.484749325	None	None	N
T/P	0.1712	likely_benign	0.1549	benign	-0.352	Destabilizing	0.999	D	0.759	deleterious	N	0.519633595	None	None	N
T/Q	0.2546	likely_benign	0.2244	benign	-0.797	Destabilizing	0.999	D	0.785	deleterious	None	None	None	None	N
T/R	0.2081	likely_benign	0.1629	benign	-0.462	Destabilizing	0.999	D	0.765	deleterious	None	None	None	None	N
T/S	0.1561	likely_benign	0.1332	benign	-0.951	Destabilizing	0.997	D	0.771	deleterious	N	0.484242346	None	None	N
T/V	0.1314	likely_benign	0.1132	benign	-0.352	Destabilizing	0.998	D	0.753	deleterious	None	None	None	None	N
T/W	0.7209	likely_pathogenic	0.6438	pathogenic	-0.797	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N
T/Y	0.3479	ambiguous	0.2914	benign	-0.559	Destabilizing	1.0	D	0.807	deleterious	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.