TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32672	98239;98240;98241	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
N2AB	31031	93316;93317;93318	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
N2A	30104	90535;90536;90537	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
N2B	23607	71044;71045;71046	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
Novex-1	23732	71419;71420;71421	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
Novex-2	23799	71620;71621;71622	chr2:178540152;178540151;178540150	chr2:179404879;179404878;179404877
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGG
• RefSeq wild type template codon: TCC
• Domain: Fn3-126
• Domain position: 73
• Structural Position: 105
• Q(SASA): 0.2995
• 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
R/S	None	None	0.961	N	0.574	0.337	0.326616659874	gnomAD-4.0.0	1.59145E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85887E-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
R/A	0.508	ambiguous	0.6131	pathogenic	-1.682	Destabilizing	0.931	D	0.577	neutral	None	None	None	None	N
R/C	0.1452	likely_benign	0.1887	benign	-1.594	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	N
R/D	0.7917	likely_pathogenic	0.8721	pathogenic	-0.516	Destabilizing	0.996	D	0.671	neutral	None	None	None	None	N
R/E	0.4783	ambiguous	0.5988	pathogenic	-0.306	Destabilizing	0.97	D	0.585	neutral	None	None	None	None	N
R/F	0.5657	likely_pathogenic	0.6446	pathogenic	-0.958	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
R/G	0.4675	ambiguous	0.6271	pathogenic	-2.058	Highly Destabilizing	0.98	D	0.584	neutral	N	0.493988576	None	None	N
R/H	0.0936	likely_benign	0.1142	benign	-1.897	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
R/I	0.2643	likely_benign	0.3138	benign	-0.608	Destabilizing	0.999	D	0.742	deleterious	None	None	None	None	N
R/K	0.0917	likely_benign	0.1079	benign	-1.236	Destabilizing	0.122	N	0.291	neutral	N	0.391322781	None	None	N
R/L	0.2353	likely_benign	0.2874	benign	-0.608	Destabilizing	0.985	D	0.584	neutral	None	None	None	None	N
R/M	0.3109	likely_benign	0.3842	ambiguous	-1.058	Destabilizing	1.0	D	0.669	neutral	N	0.462820307	None	None	N
R/N	0.5717	likely_pathogenic	0.6719	pathogenic	-1.069	Destabilizing	0.985	D	0.559	neutral	None	None	None	None	N
R/P	0.9762	likely_pathogenic	0.9862	pathogenic	-0.951	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
R/Q	0.1057	likely_benign	0.1298	benign	-1.037	Destabilizing	0.97	D	0.586	neutral	None	None	None	None	N
R/S	0.5152	ambiguous	0.6324	pathogenic	-2.032	Highly Destabilizing	0.961	D	0.574	neutral	N	0.41800795	None	None	N
R/T	0.2745	likely_benign	0.3542	ambiguous	-1.597	Destabilizing	0.98	D	0.569	neutral	N	0.425317925	None	None	N
R/V	0.3312	likely_benign	0.3929	ambiguous	-0.951	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
R/W	0.2526	likely_benign	0.3243	benign	-0.4	Destabilizing	1.0	D	0.737	prob.delet.	N	0.48535045	None	None	N
R/Y	0.3966	ambiguous	0.4873	ambiguous	-0.258	Destabilizing	0.999	D	0.731	prob.delet.	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.