TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29515	88768;88769;88770	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
N2AB	27874	83845;83846;83847	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
N2A	26947	81064;81065;81066	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
N2B	20450	61573;61574;61575	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
Novex-1	20575	61948;61949;61950	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
Novex-2	20642	62149;62150;62151	chr2:178554916;178554915;178554914	chr2:179419643;179419642;179419641
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Ig-146
• Domain position: 72
• Structural Position: 158
• Q(SASA): 0.1769
• 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
L/P	None	None	0.998	D	0.839	0.733	0.788205437025	gnomAD-4.0.0	3.1825E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.71576E-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
L/A	0.5236	ambiguous	0.5127	ambiguous	-2.192	Highly Destabilizing	0.97	D	0.691	prob.neutral	None	None	None	None	N
L/C	0.7711	likely_pathogenic	0.7754	pathogenic	-1.657	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9989	pathogenic	-1.807	Destabilizing	0.999	D	0.839	deleterious	None	None	None	None	N
L/E	0.9926	likely_pathogenic	0.9919	pathogenic	-1.721	Destabilizing	0.999	D	0.833	deleterious	None	None	None	None	N
L/F	0.8399	likely_pathogenic	0.8249	pathogenic	-1.446	Destabilizing	0.996	D	0.755	deleterious	None	None	None	None	N
L/G	0.9272	likely_pathogenic	0.919	pathogenic	-2.619	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
L/H	0.9896	likely_pathogenic	0.989	pathogenic	-1.869	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/I	0.1815	likely_benign	0.1884	benign	-1.034	Destabilizing	0.248	N	0.338	neutral	N	0.497058672	None	None	N
L/K	0.9925	likely_pathogenic	0.9923	pathogenic	-1.601	Destabilizing	0.999	D	0.83	deleterious	None	None	None	None	N
L/M	0.3456	ambiguous	0.3285	benign	-0.936	Destabilizing	0.996	D	0.762	deleterious	None	None	None	None	N
L/N	0.9911	likely_pathogenic	0.9907	pathogenic	-1.559	Destabilizing	0.999	D	0.826	deleterious	None	None	None	None	N
L/P	0.996	likely_pathogenic	0.9959	pathogenic	-1.393	Destabilizing	0.998	D	0.839	deleterious	D	0.528595087	None	None	N
L/Q	0.9666	likely_pathogenic	0.963	pathogenic	-1.641	Destabilizing	0.998	D	0.822	deleterious	N	0.489428993	None	None	N
L/R	0.9798	likely_pathogenic	0.9791	pathogenic	-1.095	Destabilizing	0.998	D	0.829	deleterious	D	0.528595087	None	None	N
L/S	0.9321	likely_pathogenic	0.9274	pathogenic	-2.294	Highly Destabilizing	0.996	D	0.818	deleterious	None	None	None	None	N
L/T	0.815	likely_pathogenic	0.8135	pathogenic	-2.075	Highly Destabilizing	0.97	D	0.755	deleterious	None	None	None	None	N
L/V	0.1389	likely_benign	0.1515	benign	-1.393	Destabilizing	0.122	N	0.33	neutral	N	0.392272504	None	None	N
L/W	0.9862	likely_pathogenic	0.9836	pathogenic	-1.593	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/Y	0.9807	likely_pathogenic	0.9783	pathogenic	-1.368	Destabilizing	0.999	D	0.785	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.