TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16105	48538;48539;48540	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
N2AB	14464	43615;43616;43617	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
N2A	13537	40834;40835;40836	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
N2B	7040	21343;21344;21345	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
Novex-1	7165	21718;21719;21720	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
Novex-2	7232	21919;21920;21921	chr2:178615788;178615787;178615786	chr2:179480515;179480514;179480513
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: Fn3-4
• Domain position: 51
• Structural Position: 68
• Q(SASA): 0.198
• 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	None	None	0.997	D	0.503	0.323	0.605825054984	gnomAD-4.0.0	1.37488E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.80289E-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	0.3593	ambiguous	0.4155	ambiguous	-1.795	Destabilizing	0.999	D	0.588	neutral	N	0.468385403	None	None	I
V/C	0.8478	likely_pathogenic	0.8604	pathogenic	-1.245	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/D	0.9036	likely_pathogenic	0.8993	pathogenic	-2.007	Highly Destabilizing	1.0	D	0.845	deleterious	D	0.670002312	None	None	I
V/E	0.8154	likely_pathogenic	0.8009	pathogenic	-1.907	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	I
V/F	0.4698	ambiguous	0.4661	ambiguous	-1.238	Destabilizing	1.0	D	0.83	deleterious	D	0.59050622	None	None	I
V/G	0.539	ambiguous	0.5585	ambiguous	-2.205	Highly Destabilizing	1.0	D	0.805	deleterious	D	0.647638866	None	None	I
V/H	0.9381	likely_pathogenic	0.9401	pathogenic	-1.718	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
V/I	0.1065	likely_benign	0.1087	benign	-0.716	Destabilizing	0.997	D	0.503	neutral	D	0.524318683	None	None	I
V/K	0.906	likely_pathogenic	0.8968	pathogenic	-1.671	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
V/L	0.4289	ambiguous	0.4534	ambiguous	-0.716	Destabilizing	0.997	D	0.564	neutral	N	0.508582449	None	None	I
V/M	0.3318	likely_benign	0.342	ambiguous	-0.567	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
V/N	0.8093	likely_pathogenic	0.8077	pathogenic	-1.702	Destabilizing	1.0	D	0.842	deleterious	None	None	None	None	I
V/P	0.9422	likely_pathogenic	0.9344	pathogenic	-1.044	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	I
V/Q	0.8443	likely_pathogenic	0.8339	pathogenic	-1.736	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	I
V/R	0.8923	likely_pathogenic	0.888	pathogenic	-1.211	Destabilizing	1.0	D	0.841	deleterious	None	None	None	None	I
V/S	0.6061	likely_pathogenic	0.6393	pathogenic	-2.235	Highly Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	I
V/T	0.4681	ambiguous	0.5101	ambiguous	-2.007	Highly Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
V/W	0.972	likely_pathogenic	0.9717	pathogenic	-1.567	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	I
V/Y	0.8748	likely_pathogenic	0.875	pathogenic	-1.226	Destabilizing	1.0	D	0.832	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.