TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30133	90622;90623;90624	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
N2AB	28492	85699;85700;85701	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
N2A	27565	82918;82919;82920	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
N2B	21068	63427;63428;63429	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
Novex-1	21193	63802;63803;63804	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
Novex-2	21260	64003;64004;64005	chr2:178552503;178552502;178552501	chr2:179417230;179417229;179417228
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-148
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.7925
• 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
L/V	None	None	0.898	D	0.547	0.244	0.46435556306	gnomAD-4.0.0	1.59263E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86164E-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	0.3828	ambiguous	0.3462	ambiguous	-1.431	Destabilizing	0.983	D	0.662	neutral	None	None	None	None	I
L/C	0.5909	likely_pathogenic	0.5349	ambiguous	-1.098	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	I
L/D	0.8391	likely_pathogenic	0.779	pathogenic	-0.695	Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	I
L/E	0.6184	likely_pathogenic	0.5705	pathogenic	-0.702	Destabilizing	0.999	D	0.74	deleterious	None	None	None	None	I
L/F	0.1855	likely_benign	0.1486	benign	-1.065	Destabilizing	0.995	D	0.725	prob.delet.	None	None	None	None	I
L/G	0.6532	likely_pathogenic	0.5954	pathogenic	-1.732	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	I
L/H	0.4117	ambiguous	0.3463	ambiguous	-0.964	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
L/I	0.0992	likely_benign	0.0908	benign	-0.694	Destabilizing	0.289	N	0.266	neutral	None	None	None	None	I
L/K	0.3866	ambiguous	0.3554	ambiguous	-0.991	Destabilizing	0.998	D	0.707	prob.neutral	None	None	None	None	I
L/M	0.1239	likely_benign	0.1168	benign	-0.652	Destabilizing	0.993	D	0.693	prob.neutral	D	0.533483619	None	None	I
L/N	0.58	likely_pathogenic	0.5152	ambiguous	-0.821	Destabilizing	0.999	D	0.743	deleterious	None	None	None	None	I
L/P	0.417	ambiguous	0.3946	ambiguous	-0.907	Destabilizing	0.999	D	0.743	deleterious	D	0.536083994	None	None	I
L/Q	0.306	likely_benign	0.2786	benign	-0.958	Destabilizing	1.0	D	0.727	prob.delet.	D	0.536083994	None	None	I
L/R	0.3357	likely_benign	0.2893	benign	-0.454	Destabilizing	0.999	D	0.735	prob.delet.	D	0.536083994	None	None	I
L/S	0.4896	ambiguous	0.4115	ambiguous	-1.431	Destabilizing	0.998	D	0.718	prob.delet.	None	None	None	None	I
L/T	0.2136	likely_benign	0.1905	benign	-1.306	Destabilizing	0.995	D	0.717	prob.delet.	None	None	None	None	I
L/V	0.1053	likely_benign	0.095	benign	-0.907	Destabilizing	0.898	D	0.547	neutral	D	0.531750035	None	None	I
L/W	0.4071	ambiguous	0.333	benign	-1.096	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
L/Y	0.4773	ambiguous	0.4076	ambiguous	-0.878	Destabilizing	0.999	D	0.746	deleterious	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.