TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31672	95239;95240;95241	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
N2AB	30031	90316;90317;90318	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
N2A	29104	87535;87536;87537	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
N2B	22607	68044;68045;68046	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
Novex-1	22732	68419;68420;68421	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
Novex-2	22799	68620;68621;68622	chr2:178546317;178546316;178546315	chr2:179411044;179411043;179411042
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-152
• Domain position: 52
• Structural Position: 137
• Q(SASA): 0.2338
• 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
T/I	rs765777016	0.174	0.002	N	0.245	0.268	0.36256342048	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	5.57E-05	None	0	None	0	0	0
T/I	rs765777016	0.174	0.002	N	0.245	0.268	0.36256342048	gnomAD-4.0.0	6.842E-07	None	None	None	None	N	None	0	0	None	0	2.51927E-05	None	0	0	0	0	0
T/S	None	None	0.6	N	0.377	0.246	0.192905019026	gnomAD-4.0.0	6.842E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99475E-07	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
T/A	0.0792	likely_benign	0.0791	benign	-1.11	Destabilizing	0.139	N	0.305	neutral	N	0.490041785	None	None	N
T/C	0.3692	ambiguous	0.332	benign	-0.902	Destabilizing	0.981	D	0.562	neutral	None	None	None	None	N
T/D	0.7332	likely_pathogenic	0.7187	pathogenic	-1.664	Destabilizing	0.936	D	0.557	neutral	None	None	None	None	N
T/E	0.471	ambiguous	0.4508	ambiguous	-1.467	Destabilizing	0.828	D	0.493	neutral	None	None	None	None	N
T/F	0.3175	likely_benign	0.2747	benign	-0.641	Destabilizing	0.704	D	0.569	neutral	None	None	None	None	N
T/G	0.3183	likely_benign	0.3217	benign	-1.534	Destabilizing	0.828	D	0.525	neutral	None	None	None	None	N
T/H	0.3444	ambiguous	0.3118	benign	-1.679	Destabilizing	0.981	D	0.57	neutral	None	None	None	None	N
T/I	0.161	likely_benign	0.1382	benign	0.003	Stabilizing	0.002	N	0.245	neutral	N	0.52036518	None	None	N
T/K	0.2894	likely_benign	0.2562	benign	-0.754	Destabilizing	0.828	D	0.495	neutral	None	None	None	None	N
T/L	0.1027	likely_benign	0.0927	benign	0.003	Stabilizing	0.085	N	0.36	neutral	None	None	None	None	N
T/M	0.0835	likely_benign	0.0748	benign	-0.025	Destabilizing	0.037	N	0.255	neutral	None	None	None	None	N
T/N	0.2347	likely_benign	0.2113	benign	-1.435	Destabilizing	0.917	D	0.499	neutral	N	0.490802253	None	None	N
T/P	0.8496	likely_pathogenic	0.8551	pathogenic	-0.336	Destabilizing	0.917	D	0.587	neutral	N	0.521023282	None	None	N
T/Q	0.267	likely_benign	0.2449	benign	-1.191	Destabilizing	0.944	D	0.578	neutral	None	None	None	None	N
T/R	0.2238	likely_benign	0.1939	benign	-0.964	Destabilizing	0.944	D	0.589	neutral	None	None	None	None	N
T/S	0.1329	likely_benign	0.1256	benign	-1.609	Destabilizing	0.6	D	0.377	neutral	N	0.450886452	None	None	N
T/V	0.1062	likely_benign	0.0961	benign	-0.336	Destabilizing	0.003	N	0.109	neutral	None	None	None	None	N
T/W	0.6939	likely_pathogenic	0.65	pathogenic	-0.843	Destabilizing	0.995	D	0.585	neutral	None	None	None	None	N
T/Y	0.4051	ambiguous	0.3495	ambiguous	-0.474	Destabilizing	0.944	D	0.599	neutral	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.