TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23518	70777;70778;70779	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
N2AB	21877	65854;65855;65856	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
N2A	20950	63073;63074;63075	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
N2B	14453	43582;43583;43584	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
Novex-1	14578	43957;43958;43959	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
Novex-2	14645	44158;44159;44160	chr2:178575580;178575579;178575578	chr2:179440307;179440306;179440305
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-58
• Domain position: 84
• Structural Position: 118
• Q(SASA): 0.1523
• 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
G/A	None	None	1.0	D	0.703	0.737	0.454426139905	gnomAD-4.0.0	1.59154E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8591E-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
G/A	0.8464	likely_pathogenic	0.8733	pathogenic	-0.861	Destabilizing	1.0	D	0.703	prob.neutral	D	0.564439679	None	None	I
G/C	0.9732	likely_pathogenic	0.9802	pathogenic	-1.064	Destabilizing	1.0	D	0.834	deleterious	D	0.554097332	None	None	I
G/D	0.9971	likely_pathogenic	0.9982	pathogenic	-1.822	Destabilizing	1.0	D	0.875	deleterious	D	0.564946658	None	None	I
G/E	0.9982	likely_pathogenic	0.9988	pathogenic	-1.916	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	I
G/F	0.9991	likely_pathogenic	0.9992	pathogenic	-1.328	Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	I
G/H	0.9987	likely_pathogenic	0.999	pathogenic	-1.334	Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	I
G/I	0.9987	likely_pathogenic	0.9991	pathogenic	-0.631	Destabilizing	1.0	D	0.882	deleterious	None	None	None	None	I
G/K	0.9994	likely_pathogenic	0.9996	pathogenic	-1.394	Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	I
G/L	0.9974	likely_pathogenic	0.9978	pathogenic	-0.631	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	I
G/M	0.9983	likely_pathogenic	0.9987	pathogenic	-0.453	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	I
G/N	0.9961	likely_pathogenic	0.9969	pathogenic	-1.086	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
G/P	0.9995	likely_pathogenic	0.9996	pathogenic	-0.67	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
G/Q	0.9978	likely_pathogenic	0.9983	pathogenic	-1.385	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
G/R	0.9977	likely_pathogenic	0.9983	pathogenic	-0.928	Destabilizing	1.0	D	0.904	deleterious	D	0.545828445	None	None	I
G/S	0.5834	likely_pathogenic	0.7201	pathogenic	-1.221	Destabilizing	1.0	D	0.813	deleterious	N	0.515660288	None	None	I
G/T	0.9689	likely_pathogenic	0.98	pathogenic	-1.262	Destabilizing	1.0	D	0.896	deleterious	None	None	None	None	I
G/V	0.9964	likely_pathogenic	0.9975	pathogenic	-0.67	Destabilizing	1.0	D	0.889	deleterious	D	0.564946658	None	None	I
G/W	0.9977	likely_pathogenic	0.9983	pathogenic	-1.599	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
G/Y	0.999	likely_pathogenic	0.9991	pathogenic	-1.244	Destabilizing	1.0	D	0.861	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.