TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33616	101071;101072;101073	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
N2AB	31975	96148;96149;96150	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
N2A	31048	93367;93368;93369	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
N2B	24551	73876;73877;73878	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
Novex-1	24676	74251;74252;74253	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
Novex-2	24743	74452;74453;74454	chr2:178535769;178535768;178535767	chr2:179400496;179400495;179400494
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-159
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.317
• 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
K/T	None	None	1.0	N	0.773	0.555	0.448696893172	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.9747	likely_pathogenic	0.9148	pathogenic	-0.572	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	N
K/C	0.9869	likely_pathogenic	0.9597	pathogenic	-0.748	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
K/D	0.9914	likely_pathogenic	0.9622	pathogenic	0.145	Stabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/E	0.9756	likely_pathogenic	0.8586	pathogenic	0.271	Stabilizing	0.998	D	0.554	neutral	N	0.470218787	None	None	N
K/F	0.9967	likely_pathogenic	0.9883	pathogenic	-0.371	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
K/G	0.9842	likely_pathogenic	0.952	pathogenic	-0.905	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
K/H	0.8891	likely_pathogenic	0.7687	pathogenic	-1.026	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/I	0.9671	likely_pathogenic	0.901	pathogenic	0.281	Stabilizing	0.996	D	0.816	deleterious	None	None	None	None	N
K/L	0.9602	likely_pathogenic	0.901	pathogenic	0.281	Stabilizing	0.996	D	0.749	deleterious	None	None	None	None	N
K/M	0.9377	likely_pathogenic	0.821	pathogenic	-0.07	Destabilizing	1.0	D	0.753	deleterious	N	0.493343013	None	None	N
K/N	0.9747	likely_pathogenic	0.9171	pathogenic	-0.469	Destabilizing	1.0	D	0.729	prob.delet.	N	0.497386746	None	None	N
K/P	0.9818	likely_pathogenic	0.9549	pathogenic	0.026	Stabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
K/Q	0.8406	likely_pathogenic	0.6158	pathogenic	-0.436	Destabilizing	0.999	D	0.705	prob.neutral	N	0.501773845	None	None	N
K/R	0.2855	likely_benign	0.2121	benign	-0.351	Destabilizing	0.997	D	0.508	neutral	N	0.479571776	None	None	N
K/S	0.9766	likely_pathogenic	0.9177	pathogenic	-1.129	Destabilizing	1.0	D	0.611	neutral	None	None	None	None	N
K/T	0.9071	likely_pathogenic	0.7212	pathogenic	-0.788	Destabilizing	1.0	D	0.773	deleterious	N	0.481417215	None	None	N
K/V	0.9535	likely_pathogenic	0.8792	pathogenic	0.026	Stabilizing	0.997	D	0.777	deleterious	None	None	None	None	N
K/W	0.9962	likely_pathogenic	0.9862	pathogenic	-0.288	Destabilizing	1.0	D	0.782	deleterious	None	None	None	None	N
K/Y	0.9884	likely_pathogenic	0.9652	pathogenic	0.019	Stabilizing	0.999	D	0.793	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.