TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30137	90634;90635;90636	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
N2AB	28496	85711;85712;85713	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
N2A	27569	82930;82931;82932	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
N2B	21072	63439;63440;63441	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
Novex-1	21197	63814;63815;63816	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
Novex-2	21264	64015;64016;64017	chr2:178552491;178552490;178552489	chr2:179417218;179417217;179417216
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-148
• Domain position: 6
• Structural Position: 7
• Q(SASA): 0.6605
• Predicted PPI site: I

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
P/L	None	None	0.885	N	0.602	0.384	0.633585262028	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
P/S	rs727505150	None	0.885	N	0.521	0.323	0.376570364461	gnomAD-4.0.0	1.36941E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80028E-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
P/A	0.0959	likely_benign	0.0884	benign	-0.381	Destabilizing	0.17	N	0.34	neutral	N	0.485159351	None	None	I
P/C	0.5396	ambiguous	0.4823	ambiguous	-0.682	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
P/D	0.5181	ambiguous	0.4732	ambiguous	-0.365	Destabilizing	0.993	D	0.559	neutral	None	None	None	None	I
P/E	0.3405	ambiguous	0.3192	benign	-0.489	Destabilizing	0.993	D	0.539	neutral	None	None	None	None	I
P/F	0.4934	ambiguous	0.4194	ambiguous	-0.701	Destabilizing	0.993	D	0.679	prob.neutral	None	None	None	None	I
P/G	0.3459	ambiguous	0.3259	benign	-0.478	Destabilizing	0.953	D	0.529	neutral	None	None	None	None	I
P/H	0.2137	likely_benign	0.1941	benign	-0.103	Destabilizing	0.999	D	0.619	neutral	N	0.514952761	None	None	I
P/I	0.2845	likely_benign	0.244	benign	-0.282	Destabilizing	0.973	D	0.643	neutral	None	None	None	None	I
P/K	0.307	likely_benign	0.3033	benign	-0.431	Destabilizing	0.993	D	0.539	neutral	None	None	None	None	I
P/L	0.1354	likely_benign	0.1196	benign	-0.282	Destabilizing	0.885	D	0.602	neutral	N	0.502417913	None	None	I
P/M	0.314	likely_benign	0.2846	benign	-0.4	Destabilizing	0.998	D	0.619	neutral	None	None	None	None	I
P/N	0.358	ambiguous	0.3342	benign	-0.21	Destabilizing	0.998	D	0.624	neutral	None	None	None	None	I
P/Q	0.1757	likely_benign	0.1719	benign	-0.454	Destabilizing	0.998	D	0.558	neutral	None	None	None	None	I
P/R	0.2183	likely_benign	0.2105	benign	0.075	Stabilizing	0.991	D	0.621	neutral	N	0.491315097	None	None	I
P/S	0.1467	likely_benign	0.1369	benign	-0.516	Destabilizing	0.885	D	0.521	neutral	N	0.482792721	None	None	I
P/T	0.1125	likely_benign	0.1021	benign	-0.544	Destabilizing	0.939	D	0.519	neutral	D	0.532998042	None	None	I
P/V	0.206	likely_benign	0.1807	benign	-0.282	Destabilizing	0.128	N	0.335	neutral	None	None	None	None	I
P/W	0.6667	likely_pathogenic	0.5985	pathogenic	-0.783	Destabilizing	0.999	D	0.68	prob.neutral	None	None	None	None	I
P/Y	0.4746	ambiguous	0.4031	ambiguous	-0.485	Destabilizing	0.998	D	0.679	prob.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.