TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34159	102700;102701;102702	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
N2AB	32518	97777;97778;97779	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
N2A	31591	94996;94997;94998	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
N2B	25094	75505;75506;75507	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
Novex-1	25219	75880;75881;75882	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
Novex-2	25286	76081;76082;76083	chr2:178534140;178534139;178534138	chr2:179398867;179398866;179398865
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-160
• Domain position: 23
• Structural Position: 35
• Q(SASA): 0.1094
• 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
I/T	rs1690397017	None	0.999	D	0.779	0.743	0.800328269811	gnomAD-4.0.0	1.59095E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85765E-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
I/A	0.9259	likely_pathogenic	0.9392	pathogenic	-2.619	Highly Destabilizing	0.996	D	0.709	prob.delet.	None	None	None	None	N
I/C	0.9888	likely_pathogenic	0.9921	pathogenic	-1.797	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
I/D	0.9964	likely_pathogenic	0.9971	pathogenic	-2.912	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/E	0.9856	likely_pathogenic	0.9882	pathogenic	-2.689	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/F	0.7806	likely_pathogenic	0.7828	pathogenic	-1.581	Destabilizing	0.217	N	0.415	neutral	N	0.489245318	None	None	N
I/G	0.9913	likely_pathogenic	0.993	pathogenic	-3.159	Highly Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/H	0.9932	likely_pathogenic	0.9944	pathogenic	-2.597	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
I/K	0.9757	likely_pathogenic	0.9797	pathogenic	-1.984	Destabilizing	1.0	D	0.83	deleterious	None	None	None	None	N
I/L	0.5045	ambiguous	0.4981	ambiguous	-1.058	Destabilizing	0.889	D	0.451	neutral	D	0.522114619	None	None	N
I/M	0.3442	ambiguous	0.3393	benign	-0.97	Destabilizing	0.999	D	0.738	prob.delet.	N	0.494271747	None	None	N
I/N	0.9572	likely_pathogenic	0.9623	pathogenic	-2.317	Highly Destabilizing	0.999	D	0.821	deleterious	D	0.536161351	None	None	N
I/P	0.9898	likely_pathogenic	0.9924	pathogenic	-1.56	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/Q	0.9829	likely_pathogenic	0.9854	pathogenic	-2.189	Highly Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
I/R	0.9682	likely_pathogenic	0.9739	pathogenic	-1.666	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
I/S	0.9518	likely_pathogenic	0.9589	pathogenic	-3.006	Highly Destabilizing	0.999	D	0.81	deleterious	D	0.523328127	None	None	N
I/T	0.8434	likely_pathogenic	0.8631	pathogenic	-2.642	Highly Destabilizing	0.999	D	0.779	deleterious	D	0.534947843	None	None	N
I/V	0.2143	likely_benign	0.2222	benign	-1.56	Destabilizing	0.941	D	0.444	neutral	N	0.44860579	None	None	N
I/W	0.9923	likely_pathogenic	0.9939	pathogenic	-1.987	Destabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
I/Y	0.9721	likely_pathogenic	0.9765	pathogenic	-1.707	Destabilizing	0.995	D	0.805	deleterious	None	None	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.