TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24408	73447;73448;73449	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
N2AB	22767	68524;68525;68526	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
N2A	21840	65743;65744;65745	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
N2B	15343	46252;46253;46254	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
Novex-1	15468	46627;46628;46629	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
Novex-2	15535	46828;46829;46830	chr2:178572910;178572909;178572908	chr2:179437637;179437636;179437635
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGG
• RefSeq wild type template codon: CCC
• Domain: Fn3-65
• Domain position: 86
• Structural Position: 118
• Q(SASA): 0.1199
• 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
G/R	rs1386903866	None	1.0	D	0.929	0.61	0.766891864429	gnomAD-4.0.0	1.59221E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43291E-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
G/A	0.7003	likely_pathogenic	0.6737	pathogenic	-0.705	Destabilizing	1.0	D	0.703	prob.neutral	D	0.537482382	None	None	N
G/C	0.9314	likely_pathogenic	0.92	pathogenic	-0.71	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
G/D	0.9835	likely_pathogenic	0.9813	pathogenic	-1.509	Destabilizing	1.0	D	0.892	deleterious	None	None	None	None	N
G/E	0.9898	likely_pathogenic	0.9881	pathogenic	-1.482	Destabilizing	1.0	D	0.926	deleterious	D	0.526379566	None	None	N
G/F	0.9975	likely_pathogenic	0.9974	pathogenic	-0.793	Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
G/H	0.9925	likely_pathogenic	0.9912	pathogenic	-1.614	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/I	0.9959	likely_pathogenic	0.9957	pathogenic	-0.057	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
G/K	0.9975	likely_pathogenic	0.9973	pathogenic	-1.24	Destabilizing	1.0	D	0.927	deleterious	None	None	None	None	N
G/L	0.9901	likely_pathogenic	0.9894	pathogenic	-0.057	Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
G/M	0.9936	likely_pathogenic	0.9932	pathogenic	-0.067	Destabilizing	1.0	D	0.875	deleterious	None	None	None	None	N
G/N	0.9845	likely_pathogenic	0.9818	pathogenic	-0.997	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
G/P	0.9986	likely_pathogenic	0.9987	pathogenic	-0.231	Destabilizing	1.0	D	0.921	deleterious	None	None	None	None	N
G/Q	0.9898	likely_pathogenic	0.9887	pathogenic	-1.058	Destabilizing	1.0	D	0.917	deleterious	None	None	None	None	N
G/R	0.9917	likely_pathogenic	0.9905	pathogenic	-1.091	Destabilizing	1.0	D	0.929	deleterious	D	0.526633056	None	None	N
G/S	0.3362	likely_benign	0.3405	ambiguous	-1.259	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/T	0.9183	likely_pathogenic	0.9184	pathogenic	-1.153	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
G/V	0.989	likely_pathogenic	0.9881	pathogenic	-0.231	Destabilizing	1.0	D	0.921	deleterious	D	0.53849634	None	None	N
G/W	0.9926	likely_pathogenic	0.9918	pathogenic	-1.374	Destabilizing	1.0	D	0.878	deleterious	D	0.53874983	None	None	N
G/Y	0.9958	likely_pathogenic	0.9953	pathogenic	-0.877	Destabilizing	1.0	D	0.891	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.