TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16304	49135;49136;49137	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
N2AB	14663	44212;44213;44214	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
N2A	13736	41431;41432;41433	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
N2B	7239	21940;21941;21942	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
Novex-1	7364	22315;22316;22317	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
Novex-2	7431	22516;22517;22518	chr2:178614604;178614603;178614602	chr2:179479331;179479330;179479329
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-110
• Domain position: 43
• Structural Position: 115
• Q(SASA): 0.2614
• 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
R/I	None	None	1.0	D	0.717	0.434	0.567858160113	gnomAD-4.0.0	2.0542E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.7998E-06	0	1.65887E-05

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
R/A	0.9342	likely_pathogenic	0.9138	pathogenic	-0.955	Destabilizing	0.999	D	0.509	neutral	None	None	None	None	N
R/C	0.5993	likely_pathogenic	0.5626	ambiguous	-0.877	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
R/D	0.9102	likely_pathogenic	0.8908	pathogenic	-0.093	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	N
R/E	0.8604	likely_pathogenic	0.8206	pathogenic	0.049	Stabilizing	0.999	D	0.571	neutral	None	None	None	None	N
R/F	0.957	likely_pathogenic	0.9486	pathogenic	-0.689	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
R/G	0.8233	likely_pathogenic	0.787	pathogenic	-1.29	Destabilizing	1.0	D	0.655	neutral	D	0.578902866	None	None	N
R/H	0.2657	likely_benign	0.2383	benign	-1.531	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
R/I	0.8662	likely_pathogenic	0.8222	pathogenic	-0.044	Destabilizing	1.0	D	0.717	prob.delet.	D	0.624805914	None	None	N
R/K	0.4543	ambiguous	0.384	ambiguous	-0.963	Destabilizing	0.997	D	0.456	neutral	N	0.50716763	None	None	N
R/L	0.8262	likely_pathogenic	0.7832	pathogenic	-0.044	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
R/M	0.879	likely_pathogenic	0.8525	pathogenic	-0.376	Destabilizing	1.0	D	0.718	prob.delet.	None	None	None	None	N
R/N	0.8022	likely_pathogenic	0.7695	pathogenic	-0.441	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
R/P	0.9714	likely_pathogenic	0.9675	pathogenic	-0.327	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
R/Q	0.3583	ambiguous	0.3225	benign	-0.564	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
R/S	0.9179	likely_pathogenic	0.8922	pathogenic	-1.257	Destabilizing	1.0	D	0.692	prob.neutral	D	0.548435402	None	None	N
R/T	0.7922	likely_pathogenic	0.7238	pathogenic	-0.922	Destabilizing	1.0	D	0.689	prob.neutral	D	0.60437028	None	None	N
R/V	0.9175	likely_pathogenic	0.8932	pathogenic	-0.327	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
R/W	0.6397	likely_pathogenic	0.618	pathogenic	-0.298	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
R/Y	0.8081	likely_pathogenic	0.7807	pathogenic	-0.029	Destabilizing	1.0	D	0.695	prob.neutral	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.