TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26572	79939;79940;79941	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
N2AB	24931	75016;75017;75018	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
N2A	24004	72235;72236;72237	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
N2B	17507	52744;52745;52746	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
Novex-1	17632	53119;53120;53121	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
Novex-2	17699	53320;53321;53322	chr2:178566418;178566417;178566416	chr2:179431145;179431144;179431143
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: Fn3-81
• Domain position: 86
• Structural Position: 118
• Q(SASA): 0.1309
• 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	0.983	N	0.696	0.531	0.281381271821	gnomAD-4.0.0	3.18391E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	2.86558E-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	0.6438	likely_pathogenic	0.6672	pathogenic	-0.881	Destabilizing	0.983	D	0.696	prob.neutral	N	0.521461133	None	None	I
G/C	0.8994	likely_pathogenic	0.9164	pathogenic	-1.003	Destabilizing	1.0	D	0.843	deleterious	D	0.533324418	None	None	I
G/D	0.9694	likely_pathogenic	0.9767	pathogenic	-1.637	Destabilizing	0.997	D	0.85	deleterious	N	0.520954154	None	None	I
G/E	0.9791	likely_pathogenic	0.984	pathogenic	-1.723	Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	I
G/F	0.996	likely_pathogenic	0.9971	pathogenic	-1.25	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	I
G/H	0.9882	likely_pathogenic	0.9917	pathogenic	-1.314	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	I
G/I	0.9931	likely_pathogenic	0.9952	pathogenic	-0.61	Destabilizing	1.0	D	0.924	deleterious	None	None	None	None	I
G/K	0.9952	likely_pathogenic	0.9968	pathogenic	-1.356	Destabilizing	0.998	D	0.912	deleterious	None	None	None	None	I
G/L	0.9873	likely_pathogenic	0.9902	pathogenic	-0.61	Destabilizing	0.998	D	0.907	deleterious	None	None	None	None	I
G/M	0.9906	likely_pathogenic	0.9925	pathogenic	-0.444	Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	I
G/N	0.9722	likely_pathogenic	0.9791	pathogenic	-1.016	Destabilizing	0.998	D	0.848	deleterious	None	None	None	None	I
G/P	0.9979	likely_pathogenic	0.9985	pathogenic	-0.663	Destabilizing	0.999	D	0.917	deleterious	None	None	None	None	I
G/Q	0.9834	likely_pathogenic	0.9876	pathogenic	-1.296	Destabilizing	0.999	D	0.919	deleterious	None	None	None	None	I
G/R	0.986	likely_pathogenic	0.9904	pathogenic	-0.918	Destabilizing	0.997	D	0.923	deleterious	N	0.521461133	None	None	I
G/S	0.2617	likely_benign	0.2663	benign	-1.203	Destabilizing	0.778	D	0.641	neutral	N	0.43244618	None	None	I
G/T	0.8606	likely_pathogenic	0.8843	pathogenic	-1.233	Destabilizing	0.996	D	0.895	deleterious	None	None	None	None	I
G/V	0.9814	likely_pathogenic	0.9857	pathogenic	-0.663	Destabilizing	0.997	D	0.904	deleterious	D	0.533577907	None	None	I
G/W	0.9867	likely_pathogenic	0.9908	pathogenic	-1.522	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	I
G/Y	0.9926	likely_pathogenic	0.995	pathogenic	-1.173	Destabilizing	1.0	D	0.911	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.