TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31843	95752;95753;95754	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
N2AB	30202	90829;90830;90831	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
N2A	29275	88048;88049;88050	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
N2B	22778	68557;68558;68559	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
Novex-1	22903	68932;68933;68934	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
Novex-2	22970	69133;69134;69135	chr2:178545583;178545582;178545581	chr2:179410310;179410309;179410308
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-120
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.201
• 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
L/P	rs1696696732	None	0.997	N	0.784	0.626	0.582449840715	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	0	2.07469E-04	0
L/P	rs1696696732	None	0.997	N	0.784	0.626	0.582449840715	gnomAD-4.0.0	6.57376E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.07469E-04	0
L/R	None	None	0.997	N	0.753	0.57	0.461323234107	gnomAD-4.0.0	1.5914E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43275E-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
L/A	0.3691	ambiguous	0.3509	ambiguous	-2.42	Highly Destabilizing	0.953	D	0.604	neutral	None	None	None	None	N
L/C	0.4784	ambiguous	0.4677	ambiguous	-1.676	Destabilizing	0.999	D	0.664	neutral	None	None	None	None	N
L/D	0.8902	likely_pathogenic	0.8774	pathogenic	-2.704	Highly Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	N
L/E	0.5698	likely_pathogenic	0.5563	ambiguous	-2.636	Highly Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
L/F	0.1459	likely_benign	0.1399	benign	-1.647	Destabilizing	0.986	D	0.648	neutral	None	None	None	None	N
L/G	0.835	likely_pathogenic	0.8027	pathogenic	-2.807	Highly Destabilizing	0.998	D	0.77	deleterious	None	None	None	None	N
L/H	0.2779	likely_benign	0.2618	benign	-1.989	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
L/I	0.0758	likely_benign	0.0781	benign	-1.365	Destabilizing	0.046	N	0.387	neutral	N	0.342800902	None	None	N
L/K	0.4943	ambiguous	0.4843	ambiguous	-1.854	Destabilizing	0.993	D	0.739	prob.delet.	None	None	None	None	N
L/M	0.1028	likely_benign	0.098	benign	-1.123	Destabilizing	0.986	D	0.685	prob.neutral	None	None	None	None	N
L/N	0.5831	likely_pathogenic	0.5711	pathogenic	-1.865	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
L/P	0.9875	likely_pathogenic	0.9882	pathogenic	-1.693	Destabilizing	0.997	D	0.784	deleterious	N	0.477889698	None	None	N
L/Q	0.2316	likely_benign	0.2129	benign	-2.017	Highly Destabilizing	0.997	D	0.742	deleterious	N	0.477786972	None	None	N
L/R	0.3608	ambiguous	0.3332	benign	-1.186	Destabilizing	0.997	D	0.753	deleterious	N	0.449637579	None	None	N
L/S	0.4283	ambiguous	0.4017	ambiguous	-2.453	Highly Destabilizing	0.993	D	0.723	prob.delet.	None	None	None	None	N
L/T	0.264	likely_benign	0.2483	benign	-2.276	Highly Destabilizing	0.986	D	0.642	neutral	None	None	None	None	N
L/V	0.0828	likely_benign	0.0845	benign	-1.693	Destabilizing	0.17	N	0.502	neutral	N	0.385820961	None	None	N
L/W	0.2951	likely_benign	0.2724	benign	-1.844	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
L/Y	0.3821	ambiguous	0.3637	ambiguous	-1.654	Destabilizing	0.998	D	0.696	prob.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.