TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30332	91219;91220;91221	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
N2AB	28691	86296;86297;86298	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
N2A	27764	83515;83516;83517	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
N2B	21267	64024;64025;64026	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
Novex-1	21392	64399;64400;64401	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
Novex-2	21459	64600;64601;64602	chr2:178551906;178551905;178551904	chr2:179416633;179416632;179416631
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-109
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4724
• 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
V/I	None	None	0.997	N	0.481	0.175	0.593798965771	gnomAD-4.0.0	1.36843E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79899E-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
V/A	0.2089	likely_benign	0.1757	benign	-1.107	Destabilizing	0.999	D	0.569	neutral	N	0.492852425	None	None	I
V/C	0.6942	likely_pathogenic	0.6593	pathogenic	-0.69	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
V/D	0.4349	ambiguous	0.3729	ambiguous	-0.787	Destabilizing	1.0	D	0.877	deleterious	N	0.509726033	None	None	I
V/E	0.3395	likely_benign	0.2821	benign	-0.762	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	I
V/F	0.1629	likely_benign	0.152	benign	-0.682	Destabilizing	1.0	D	0.835	deleterious	N	0.490217552	None	None	I
V/G	0.2942	likely_benign	0.2586	benign	-1.428	Destabilizing	1.0	D	0.851	deleterious	N	0.479344502	None	None	I
V/H	0.5105	ambiguous	0.449	ambiguous	-0.931	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	I
V/I	0.0741	likely_benign	0.0716	benign	-0.325	Destabilizing	0.997	D	0.481	neutral	N	0.480712634	None	None	I
V/K	0.4224	ambiguous	0.3553	ambiguous	-0.976	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	I
V/L	0.1761	likely_benign	0.1605	benign	-0.325	Destabilizing	0.997	D	0.508	neutral	N	0.457182414	None	None	I
V/M	0.1257	likely_benign	0.1188	benign	-0.304	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	I
V/N	0.2427	likely_benign	0.203	benign	-0.849	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	I
V/P	0.9411	likely_pathogenic	0.9156	pathogenic	-0.55	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
V/Q	0.3022	likely_benign	0.2553	benign	-0.941	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	I
V/R	0.3874	ambiguous	0.3298	benign	-0.54	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	I
V/S	0.207	likely_benign	0.1759	benign	-1.371	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	I
V/T	0.1855	likely_benign	0.1552	benign	-1.233	Destabilizing	0.999	D	0.641	neutral	None	None	None	None	I
V/W	0.8118	likely_pathogenic	0.7781	pathogenic	-0.927	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	I
V/Y	0.4766	ambiguous	0.4373	ambiguous	-0.599	Destabilizing	1.0	D	0.837	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.