TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35316	106171;106172;106173	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
N2AB	33675	101248;101249;101250	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
N2A	32748	98467;98468;98469	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
N2B	26251	78976;78977;78978	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
Novex-1	26376	79351;79352;79353	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
Novex-2	26443	79552;79553;79554	chr2:178530669;178530668;178530667	chr2:179395396;179395395;179395394
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-165
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.7818
• 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
E/Q	None	None	1.0	N	0.625	0.264	0.460264052551	gnomAD-4.0.0	1.59086E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85745E-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
E/A	0.2486	likely_benign	0.2393	benign	-0.422	Destabilizing	0.999	D	0.687	prob.neutral	D	0.531790108	None	None	I
E/C	0.9572	likely_pathogenic	0.9516	pathogenic	-0.073	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
E/D	0.1848	likely_benign	0.1741	benign	-0.37	Destabilizing	0.999	D	0.507	neutral	N	0.521303755	None	None	I
E/F	0.9031	likely_pathogenic	0.897	pathogenic	-0.28	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
E/G	0.3023	likely_benign	0.2814	benign	-0.628	Destabilizing	1.0	D	0.697	prob.neutral	N	0.50505494	None	None	I
E/H	0.7182	likely_pathogenic	0.6959	pathogenic	-0.082	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/I	0.6337	likely_pathogenic	0.6063	pathogenic	0.089	Stabilizing	1.0	D	0.78	deleterious	None	None	None	None	I
E/K	0.2999	likely_benign	0.2766	benign	0.283	Stabilizing	0.999	D	0.607	neutral	N	0.49034613	None	None	I
E/L	0.7291	likely_pathogenic	0.7022	pathogenic	0.089	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
E/M	0.7031	likely_pathogenic	0.6766	pathogenic	0.19	Stabilizing	1.0	D	0.743	deleterious	None	None	None	None	I
E/N	0.3745	ambiguous	0.3431	ambiguous	-0.062	Destabilizing	1.0	D	0.728	prob.delet.	None	None	None	None	I
E/P	0.9076	likely_pathogenic	0.9019	pathogenic	-0.061	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
E/Q	0.2951	likely_benign	0.2749	benign	-0.023	Destabilizing	1.0	D	0.625	neutral	N	0.510452043	None	None	I
E/R	0.5128	ambiguous	0.4818	ambiguous	0.485	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/S	0.3483	ambiguous	0.326	benign	-0.223	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	I
E/T	0.3485	ambiguous	0.3231	benign	-0.054	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
E/V	0.3754	ambiguous	0.3595	ambiguous	-0.061	Destabilizing	1.0	D	0.751	deleterious	N	0.519476958	None	None	I
E/W	0.9671	likely_pathogenic	0.9632	pathogenic	-0.119	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
E/Y	0.8209	likely_pathogenic	0.8097	pathogenic	-0.036	Destabilizing	1.0	D	0.76	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.