TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24365	73318;73319;73320	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
N2AB	22724	68395;68396;68397	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
N2A	21797	65614;65615;65616	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
N2B	15300	46123;46124;46125	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
Novex-1	15425	46498;46499;46500	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
Novex-2	15492	46699;46700;46701	chr2:178573039;178573038;178573037	chr2:179437766;179437765;179437764
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-65
• Domain position: 43
• Structural Position: 50
• Q(SASA): 0.3288
• 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
P/S	None	None	0.805	N	0.521	0.271	0.285316908763	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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
P/A	0.0859	likely_benign	0.0838	benign	-1.333	Destabilizing	0.025	N	0.382	neutral	N	0.393514937	None	None	N
P/C	0.5286	ambiguous	0.506	ambiguous	-0.766	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
P/D	0.5496	ambiguous	0.5272	ambiguous	-1.286	Destabilizing	0.975	D	0.553	neutral	None	None	None	None	N
P/E	0.3129	likely_benign	0.305	benign	-1.339	Destabilizing	0.975	D	0.533	neutral	None	None	None	None	N
P/F	0.6197	likely_pathogenic	0.5649	pathogenic	-1.191	Destabilizing	0.987	D	0.724	prob.delet.	None	None	None	None	N
P/G	0.3219	likely_benign	0.3079	benign	-1.594	Destabilizing	0.845	D	0.585	neutral	None	None	None	None	N
P/H	0.3059	likely_benign	0.2845	benign	-1.152	Destabilizing	0.154	N	0.537	neutral	None	None	None	None	N
P/I	0.3143	likely_benign	0.2941	benign	-0.738	Destabilizing	0.975	D	0.732	prob.delet.	None	None	None	None	N
P/K	0.3096	likely_benign	0.3109	benign	-1.183	Destabilizing	0.975	D	0.537	neutral	None	None	None	None	N
P/L	0.1233	likely_benign	0.1141	benign	-0.738	Destabilizing	0.967	D	0.676	prob.neutral	N	0.465415108	None	None	N
P/M	0.3359	likely_benign	0.3101	benign	-0.451	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
P/N	0.4093	ambiguous	0.4	ambiguous	-0.847	Destabilizing	0.975	D	0.681	prob.neutral	None	None	None	None	N
P/Q	0.2175	likely_benign	0.2027	benign	-1.095	Destabilizing	0.967	D	0.604	neutral	N	0.477978974	None	None	N
P/R	0.2442	likely_benign	0.2309	benign	-0.558	Destabilizing	0.967	D	0.683	prob.neutral	N	0.478499049	None	None	N
P/S	0.1606	likely_benign	0.1508	benign	-1.271	Destabilizing	0.805	D	0.521	neutral	N	0.451869808	None	None	N
P/T	0.1238	likely_benign	0.1151	benign	-1.229	Destabilizing	0.967	D	0.525	neutral	N	0.462201445	None	None	N
P/V	0.2008	likely_benign	0.1905	benign	-0.902	Destabilizing	0.95	D	0.605	neutral	None	None	None	None	N
P/W	0.7521	likely_pathogenic	0.7117	pathogenic	-1.337	Destabilizing	0.999	D	0.731	prob.delet.	None	None	None	None	N
P/Y	0.5924	likely_pathogenic	0.5577	ambiguous	-1.079	Destabilizing	0.95	D	0.735	prob.delet.	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.