TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21451	64576;64577;64578	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
N2AB	19810	59653;59654;59655	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
N2A	18883	56872;56873;56874	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
N2B	12386	37381;37382;37383	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
Novex-1	12511	37756;37757;37758	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
Novex-2	12578	37957;37958;37959	chr2:178586550;178586549;178586548	chr2:179451277;179451276;179451275
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-43
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.6866
• 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
L/F	rs1576014111	None	0.004	N	0.277	0.114	0.429203605099	gnomAD-4.0.0	6.84458E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99769E-07	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
L/A	0.245	likely_benign	0.2543	benign	-0.651	Destabilizing	0.25	N	0.64	neutral	None	None	None	None	I
L/C	0.67	likely_pathogenic	0.6856	pathogenic	-0.62	Destabilizing	0.982	D	0.717	prob.delet.	None	None	None	None	I
L/D	0.7177	likely_pathogenic	0.6764	pathogenic	-0.231	Destabilizing	0.826	D	0.763	deleterious	None	None	None	None	I
L/E	0.4067	ambiguous	0.362	ambiguous	-0.329	Destabilizing	0.826	D	0.769	deleterious	None	None	None	None	I
L/F	0.2181	likely_benign	0.2015	benign	-0.704	Destabilizing	0.004	N	0.277	neutral	N	0.519420164	None	None	I
L/G	0.5836	likely_pathogenic	0.5943	pathogenic	-0.805	Destabilizing	0.7	D	0.77	deleterious	None	None	None	None	I
L/H	0.3375	likely_benign	0.3349	benign	-0.084	Destabilizing	0.982	D	0.745	deleterious	None	None	None	None	I
L/I	0.1426	likely_benign	0.1319	benign	-0.37	Destabilizing	0.25	N	0.561	neutral	None	None	None	None	I
L/K	0.2809	likely_benign	0.2705	benign	-0.348	Destabilizing	0.7	D	0.753	deleterious	None	None	None	None	I
L/M	0.1304	likely_benign	0.1455	benign	-0.399	Destabilizing	0.034	N	0.431	neutral	N	0.514475704	None	None	I
L/N	0.4126	ambiguous	0.3929	ambiguous	-0.135	Destabilizing	0.826	D	0.762	deleterious	None	None	None	None	I
L/P	0.2441	likely_benign	0.2423	benign	-0.431	Destabilizing	0.935	D	0.765	deleterious	None	None	None	None	I
L/Q	0.185	likely_benign	0.185	benign	-0.375	Destabilizing	0.7	D	0.741	deleterious	None	None	None	None	I
L/R	0.2814	likely_benign	0.282	benign	0.228	Stabilizing	0.7	D	0.746	deleterious	None	None	None	None	I
L/S	0.311	likely_benign	0.3155	benign	-0.579	Destabilizing	0.638	D	0.738	prob.delet.	N	0.468913986	None	None	I
L/T	0.2985	likely_benign	0.2938	benign	-0.568	Destabilizing	0.7	D	0.694	prob.neutral	None	None	None	None	I
L/V	0.1256	likely_benign	0.1225	benign	-0.431	Destabilizing	0.201	N	0.571	neutral	N	0.48407544	None	None	I
L/W	0.419	ambiguous	0.4032	ambiguous	-0.706	Destabilizing	0.976	D	0.737	prob.delet.	N	0.487329765	None	None	I
L/Y	0.4366	ambiguous	0.4009	ambiguous	-0.459	Destabilizing	0.539	D	0.752	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.