TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13732	41419;41420;41421	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
N2AB	12091	36496;36497;36498	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
N2A	11164	33715;33716;33717	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
N2B	4667	14224;14225;14226	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
Novex-1	4792	14599;14600;14601	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
Novex-2	4859	14800;14801;14802	chr2:178636533;178636532;178636531	chr2:179501260;179501259;179501258
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-87
• Domain position: 49
• Structural Position: 121
• Q(SASA): 0.2576
• 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
H/N	None	None	0.999	N	0.476	0.407	0.340032825777	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88274E-05	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
H/A	0.9123	likely_pathogenic	0.9632	pathogenic	-1.82	Destabilizing	0.999	D	0.628	neutral	None	None	None	None	N
H/C	0.4846	ambiguous	0.5667	pathogenic	-1.003	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
H/D	0.9534	likely_pathogenic	0.9834	pathogenic	-1.729	Destabilizing	1.0	D	0.698	prob.neutral	N	0.513363795	None	None	N
H/E	0.9269	likely_pathogenic	0.9761	pathogenic	-1.52	Destabilizing	0.999	D	0.466	neutral	None	None	None	None	N
H/F	0.3661	ambiguous	0.5685	pathogenic	0.161	Stabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
H/G	0.9481	likely_pathogenic	0.9823	pathogenic	-2.262	Highly Destabilizing	0.999	D	0.669	neutral	None	None	None	None	N
H/I	0.6296	likely_pathogenic	0.8201	pathogenic	-0.508	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
H/K	0.9303	likely_pathogenic	0.9698	pathogenic	-1.173	Destabilizing	1.0	D	0.692	prob.neutral	None	None	None	None	N
H/L	0.3419	ambiguous	0.5465	ambiguous	-0.508	Destabilizing	1.0	D	0.777	deleterious	N	0.498608509	None	None	N
H/M	0.7766	likely_pathogenic	0.8911	pathogenic	-0.72	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
H/N	0.5187	ambiguous	0.728	pathogenic	-1.904	Destabilizing	0.999	D	0.476	neutral	N	0.512721423	None	None	N
H/P	0.9704	likely_pathogenic	0.9842	pathogenic	-0.936	Destabilizing	1.0	D	0.806	deleterious	N	0.510642928	None	None	N
H/Q	0.7662	likely_pathogenic	0.9113	pathogenic	-1.467	Destabilizing	1.0	D	0.669	neutral	N	0.510637132	None	None	N
H/R	0.7805	likely_pathogenic	0.9032	pathogenic	-1.423	Destabilizing	1.0	D	0.623	neutral	N	0.511917922	None	None	N
H/S	0.8364	likely_pathogenic	0.93	pathogenic	-2.047	Highly Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
H/T	0.8097	likely_pathogenic	0.9233	pathogenic	-1.714	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	N
H/V	0.5741	likely_pathogenic	0.7733	pathogenic	-0.936	Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
H/W	0.5758	likely_pathogenic	0.7217	pathogenic	0.764	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
H/Y	0.0976	likely_benign	0.1705	benign	0.55	Stabilizing	0.999	D	0.526	neutral	N	0.438473263	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.