TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27170	81733;81734;81735	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
N2AB	25529	76810;76811;76812	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
N2A	24602	74029;74030;74031	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
N2B	18105	54538;54539;54540	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
Novex-1	18230	54913;54914;54915	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
Novex-2	18297	55114;55115;55116	chr2:178564624;178564623;178564622	chr2:179429351;179429350;179429349
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-86
• Domain position: 1
• Structural Position: 1
• Q(SASA): 0.9802
• 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
P/L	rs774553407	0.333	0.986	N	0.657	0.482	0.663099739152	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
P/L	rs774553407	0.333	0.986	N	0.657	0.482	0.663099739152	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43283E-05	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	0.132	likely_benign	0.1194	benign	-0.234	Destabilizing	0.058	N	0.372	neutral	N	0.515015898	None	None	N
P/C	0.6692	likely_pathogenic	0.6528	pathogenic	-0.39	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	N
P/D	0.7594	likely_pathogenic	0.7492	pathogenic	-0.231	Destabilizing	0.995	D	0.707	prob.delet.	None	None	None	None	N
P/E	0.539	ambiguous	0.5316	ambiguous	-0.367	Destabilizing	0.989	D	0.693	prob.delet.	None	None	None	None	N
P/F	0.7255	likely_pathogenic	0.6979	pathogenic	-0.659	Destabilizing	0.999	D	0.792	deleterious	None	None	None	None	N
P/G	0.612	likely_pathogenic	0.601	pathogenic	-0.329	Destabilizing	0.929	D	0.717	prob.delet.	None	None	None	None	N
P/H	0.3785	ambiguous	0.3907	ambiguous	-0.022	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
P/I	0.4445	ambiguous	0.4194	ambiguous	-0.144	Destabilizing	0.989	D	0.758	deleterious	None	None	None	None	N
P/K	0.4524	ambiguous	0.476	ambiguous	-0.156	Destabilizing	0.989	D	0.699	prob.delet.	None	None	None	None	N
P/L	0.2153	likely_benign	0.1939	benign	-0.144	Destabilizing	0.986	D	0.657	prob.neutral	N	0.496151175	None	None	N
P/M	0.5076	ambiguous	0.4921	ambiguous	-0.177	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
P/N	0.589	likely_pathogenic	0.5944	pathogenic	0.195	Stabilizing	0.995	D	0.818	deleterious	None	None	None	None	N
P/Q	0.2958	likely_benign	0.3133	benign	-0.088	Destabilizing	0.993	D	0.713	prob.delet.	D	0.529071683	None	None	N
P/R	0.2877	likely_benign	0.2935	benign	0.329	Stabilizing	0.993	D	0.805	deleterious	N	0.500799211	None	None	N
P/S	0.2595	likely_benign	0.2501	benign	-0.117	Destabilizing	0.972	D	0.725	deleterious	N	0.484215893	None	None	N
P/T	0.2102	likely_benign	0.2054	benign	-0.158	Destabilizing	0.986	D	0.662	prob.neutral	D	0.528057725	None	None	N
P/V	0.3158	likely_benign	0.2975	benign	-0.14	Destabilizing	0.979	D	0.679	prob.neutral	None	None	None	None	N
P/W	0.8854	likely_pathogenic	0.8749	pathogenic	-0.735	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	N
P/Y	0.7116	likely_pathogenic	0.7023	pathogenic	-0.406	Destabilizing	1.0	D	0.786	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.