TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24413	73462;73463;73464	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
N2AB	22772	68539;68540;68541	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
N2A	21845	65758;65759;65760	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
N2B	15348	46267;46268;46269	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
Novex-1	15473	46642;46643;46644	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
Novex-2	15540	46843;46844;46845	chr2:178572895;178572894;178572893	chr2:179437622;179437621;179437620
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: Fn3-65
• Domain position: 91
• Structural Position: 123
• Q(SASA): 0.1754
• 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
V/F	None	None	0.931	N	0.665	0.325	0.664136802156	gnomAD-4.0.0	1.59214E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85953E-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	0.7203	likely_pathogenic	0.6832	pathogenic	-1.514	Destabilizing	0.792	D	0.665	prob.neutral	N	0.51950867	None	None	N
V/C	0.8982	likely_pathogenic	0.8717	pathogenic	-1.06	Destabilizing	0.998	D	0.647	neutral	None	None	None	None	N
V/D	0.9872	likely_pathogenic	0.9842	pathogenic	-1.458	Destabilizing	0.988	D	0.851	deleterious	N	0.510910155	None	None	N
V/E	0.9669	likely_pathogenic	0.958	pathogenic	-1.364	Destabilizing	0.973	D	0.719	prob.delet.	None	None	None	None	N
V/F	0.6036	likely_pathogenic	0.5172	ambiguous	-0.922	Destabilizing	0.931	D	0.665	prob.neutral	N	0.48906969	None	None	N
V/G	0.8777	likely_pathogenic	0.8467	pathogenic	-1.932	Destabilizing	0.964	D	0.838	deleterious	D	0.522177555	None	None	N
V/H	0.9844	likely_pathogenic	0.9778	pathogenic	-1.595	Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	N
V/I	0.087	likely_benign	0.0834	benign	-0.427	Destabilizing	0.049	N	0.246	neutral	N	0.48468402	None	None	N
V/K	0.9836	likely_pathogenic	0.9782	pathogenic	-1.387	Destabilizing	0.973	D	0.729	deleterious	None	None	None	None	N
V/L	0.3452	ambiguous	0.2915	benign	-0.427	Destabilizing	0.012	N	0.296	neutral	N	0.477333973	None	None	N
V/M	0.4925	ambiguous	0.4276	ambiguous	-0.395	Destabilizing	0.947	D	0.633	neutral	None	None	None	None	N
V/N	0.9619	likely_pathogenic	0.9522	pathogenic	-1.347	Destabilizing	0.991	D	0.829	deleterious	None	None	None	None	N
V/P	0.899	likely_pathogenic	0.8959	pathogenic	-0.755	Destabilizing	0.991	D	0.727	deleterious	None	None	None	None	N
V/Q	0.962	likely_pathogenic	0.9503	pathogenic	-1.349	Destabilizing	0.991	D	0.707	prob.delet.	None	None	None	None	N
V/R	0.9743	likely_pathogenic	0.9663	pathogenic	-1.065	Destabilizing	0.973	D	0.836	deleterious	None	None	None	None	N
V/S	0.8737	likely_pathogenic	0.8486	pathogenic	-1.921	Destabilizing	0.973	D	0.724	deleterious	None	None	None	None	N
V/T	0.7805	likely_pathogenic	0.7495	pathogenic	-1.698	Destabilizing	0.835	D	0.629	neutral	None	None	None	None	N
V/W	0.9876	likely_pathogenic	0.9795	pathogenic	-1.27	Destabilizing	0.998	D	0.751	deleterious	None	None	None	None	N
V/Y	0.9522	likely_pathogenic	0.9288	pathogenic	-0.91	Destabilizing	0.973	D	0.606	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.