TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4729	14410;14411;14412	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
N2AB	4412	13459;13460;13461	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
N2A	3485	10678;10679;10680	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
N2B	4366	13321;13322;13323	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
Novex-1	4491	13696;13697;13698	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
Novex-2	4558	13897;13898;13899	chr2:178738268;178738267;178738266	chr2:179602995;179602994;179602993
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTC
• RefSeq wild type template codon: CAG
• Domain: Ig-30
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1717
• 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	rs1279065978	-0.627	0.898	N	0.556	0.239	0.486209434461	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	5.61E-05	None	0	None	0	0	0
V/I	rs1279065978	-0.627	0.898	N	0.556	0.239	0.486209434461	gnomAD-4.0.0	1.59192E-06	None	None	None	None	I	None	0	0	None	0	2.78195E-05	None	0	0	0	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	0.4111	ambiguous	0.5199	ambiguous	-1.754	Destabilizing	0.977	D	0.513	neutral	N	0.478388083	None	None	I
V/C	0.8642	likely_pathogenic	0.904	pathogenic	-1.197	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
V/D	0.9349	likely_pathogenic	0.9611	pathogenic	-1.963	Destabilizing	0.999	D	0.829	deleterious	N	0.443703351	None	None	I
V/E	0.8601	likely_pathogenic	0.9044	pathogenic	-1.828	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	I
V/F	0.5713	likely_pathogenic	0.7429	pathogenic	-1.144	Destabilizing	0.993	D	0.795	deleterious	N	0.478735164	None	None	I
V/G	0.593	likely_pathogenic	0.7105	pathogenic	-2.217	Highly Destabilizing	0.999	D	0.811	deleterious	N	0.479640412	None	None	I
V/H	0.9579	likely_pathogenic	0.9772	pathogenic	-1.987	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
V/I	0.1131	likely_benign	0.127	benign	-0.513	Destabilizing	0.898	D	0.556	neutral	N	0.477807057	None	None	I
V/K	0.9125	likely_pathogenic	0.9435	pathogenic	-1.456	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	I
V/L	0.4789	ambiguous	0.6161	pathogenic	-0.513	Destabilizing	0.117	N	0.285	neutral	N	0.474423849	None	None	I
V/M	0.4044	ambiguous	0.5254	ambiguous	-0.435	Destabilizing	0.995	D	0.757	deleterious	None	None	None	None	I
V/N	0.8545	likely_pathogenic	0.9069	pathogenic	-1.515	Destabilizing	0.999	D	0.822	deleterious	None	None	None	None	I
V/P	0.7977	likely_pathogenic	0.8578	pathogenic	-0.895	Destabilizing	0.999	D	0.811	deleterious	None	None	None	None	I
V/Q	0.877	likely_pathogenic	0.9209	pathogenic	-1.479	Destabilizing	0.999	D	0.805	deleterious	None	None	None	None	I
V/R	0.8769	likely_pathogenic	0.9178	pathogenic	-1.191	Destabilizing	0.998	D	0.827	deleterious	None	None	None	None	I
V/S	0.6246	likely_pathogenic	0.732	pathogenic	-2.111	Highly Destabilizing	0.998	D	0.793	deleterious	None	None	None	None	I
V/T	0.4619	ambiguous	0.5516	ambiguous	-1.844	Destabilizing	0.991	D	0.662	neutral	None	None	None	None	I
V/W	0.9771	likely_pathogenic	0.9905	pathogenic	-1.586	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
V/Y	0.9161	likely_pathogenic	0.9572	pathogenic	-1.192	Destabilizing	0.999	D	0.795	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.