TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20781	62566;62567;62568	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
N2AB	19140	57643;57644;57645	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
N2A	18213	54862;54863;54864	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
N2B	11716	35371;35372;35373	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
Novex-1	11841	35746;35747;35748	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
Novex-2	11908	35947;35948;35949	chr2:178589384;178589383;178589382	chr2:179454111;179454110;179454109
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-122
• Domain position: 13
• Structural Position: 16
• Q(SASA): 0.9202
• 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/F	None	None	1.0	D	0.568	0.748	0.895171775139	gnomAD-4.0.0	1.59198E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43299E-05	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	0.5418	ambiguous	0.5856	pathogenic	-1.865	Destabilizing	0.999	D	0.535	neutral	N	0.496352169	None	None	I
V/C	0.8577	likely_pathogenic	0.8834	pathogenic	-1.359	Destabilizing	1.0	D	0.577	neutral	None	None	None	None	I
V/D	0.988	likely_pathogenic	0.9899	pathogenic	-1.893	Destabilizing	1.0	D	0.629	neutral	D	0.547284747	None	None	I
V/E	0.9423	likely_pathogenic	0.9503	pathogenic	-1.823	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	I
V/F	0.5991	likely_pathogenic	0.6607	pathogenic	-1.305	Destabilizing	1.0	D	0.568	neutral	D	0.523647083	None	None	I
V/G	0.7915	likely_pathogenic	0.8127	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.599	neutral	D	0.540029818	None	None	I
V/H	0.9776	likely_pathogenic	0.9832	pathogenic	-1.83	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
V/I	0.1018	likely_benign	0.1141	benign	-0.811	Destabilizing	0.997	D	0.545	neutral	N	0.517612876	None	None	I
V/K	0.9395	likely_pathogenic	0.9453	pathogenic	-1.552	Destabilizing	1.0	D	0.555	neutral	None	None	None	None	I
V/L	0.4733	ambiguous	0.5296	ambiguous	-0.811	Destabilizing	0.997	D	0.575	neutral	N	0.496424567	None	None	I
V/M	0.441	ambiguous	0.5085	ambiguous	-0.678	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	I
V/N	0.9573	likely_pathogenic	0.9648	pathogenic	-1.472	Destabilizing	1.0	D	0.636	neutral	None	None	None	None	I
V/P	0.989	likely_pathogenic	0.9906	pathogenic	-1.13	Destabilizing	1.0	D	0.584	neutral	None	None	None	None	I
V/Q	0.9076	likely_pathogenic	0.9224	pathogenic	-1.557	Destabilizing	1.0	D	0.599	neutral	None	None	None	None	I
V/R	0.9134	likely_pathogenic	0.9214	pathogenic	-1.105	Destabilizing	1.0	D	0.639	neutral	None	None	None	None	I
V/S	0.8328	likely_pathogenic	0.8604	pathogenic	-2.072	Highly Destabilizing	1.0	D	0.563	neutral	None	None	None	None	I
V/T	0.6571	likely_pathogenic	0.685	pathogenic	-1.883	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	I
V/W	0.9889	likely_pathogenic	0.9924	pathogenic	-1.594	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
V/Y	0.9427	likely_pathogenic	0.9604	pathogenic	-1.289	Destabilizing	1.0	D	0.576	neutral	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.