TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30442	91549;91550;91551	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
N2AB	28801	86626;86627;86628	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
N2A	27874	83845;83846;83847	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
N2B	21377	64354;64355;64356	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
Novex-1	21502	64729;64730;64731	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
Novex-2	21569	64930;64931;64932	chr2:178551207;178551206;178551205	chr2:179415934;179415933;179415932
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Fn3-110
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.283
• 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	rs370086155	-1.048	0.98	N	0.545	0.463	None	gnomAD-2.1.1	1.43E-05	None	None	None	None	N	None	1.65344E-04	0	None	0	0	None	0	None	0	0	0
K/T	rs370086155	-1.048	0.98	N	0.545	0.463	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	N	None	2.17255E-04	0	0	0	0	None	0	0	0	0	0
K/T	rs370086155	-1.048	0.98	N	0.545	0.463	None	gnomAD-4.0.0	1.30159E-05	None	None	None	None	N	None	2.67094E-04	0	None	0	0	None	0	0	0	0	1.60128E-05

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	0.6197	likely_pathogenic	0.6628	pathogenic	-0.888	Destabilizing	0.97	D	0.491	neutral	None	None	None	None	N
K/C	0.705	likely_pathogenic	0.7134	pathogenic	-0.778	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
K/D	0.9344	likely_pathogenic	0.9386	pathogenic	-0.615	Destabilizing	0.97	D	0.528	neutral	None	None	None	None	N
K/E	0.4856	ambiguous	0.5314	ambiguous	-0.431	Destabilizing	0.835	D	0.433	neutral	N	0.442692964	None	None	N
K/F	0.9029	likely_pathogenic	0.907	pathogenic	-0.222	Destabilizing	0.999	D	0.735	prob.delet.	None	None	None	None	N
K/G	0.8133	likely_pathogenic	0.8337	pathogenic	-1.333	Destabilizing	0.985	D	0.566	neutral	None	None	None	None	N
K/H	0.4414	ambiguous	0.4448	ambiguous	-1.602	Destabilizing	0.996	D	0.681	prob.neutral	None	None	None	None	N
K/I	0.5246	ambiguous	0.5527	ambiguous	0.315	Stabilizing	0.998	D	0.725	prob.delet.	N	0.491276345	None	None	N
K/L	0.5346	ambiguous	0.5778	pathogenic	0.315	Stabilizing	0.97	D	0.566	neutral	None	None	None	None	N
K/M	0.3595	ambiguous	0.3935	ambiguous	0.144	Stabilizing	0.999	D	0.682	prob.neutral	None	None	None	None	N
K/N	0.7969	likely_pathogenic	0.8179	pathogenic	-0.958	Destabilizing	0.98	D	0.446	neutral	N	0.497527526	None	None	N
K/P	0.9905	likely_pathogenic	0.9921	pathogenic	-0.058	Destabilizing	0.999	D	0.594	neutral	None	None	None	None	N
K/Q	0.1645	likely_benign	0.1852	benign	-0.859	Destabilizing	0.489	N	0.29	neutral	N	0.43388148	None	None	N
K/R	0.0941	likely_benign	0.0956	benign	-0.933	Destabilizing	0.961	D	0.415	neutral	N	0.441519528	None	None	N
K/S	0.6694	likely_pathogenic	0.7099	pathogenic	-1.577	Destabilizing	0.97	D	0.371	neutral	None	None	None	None	N
K/T	0.3391	likely_benign	0.3702	ambiguous	-1.162	Destabilizing	0.98	D	0.545	neutral	N	0.434534841	None	None	N
K/V	0.472	ambiguous	0.5109	ambiguous	-0.058	Destabilizing	0.996	D	0.605	neutral	None	None	None	None	N
K/W	0.8793	likely_pathogenic	0.8844	pathogenic	-0.148	Destabilizing	1.0	D	0.704	prob.neutral	None	None	None	None	N
K/Y	0.8027	likely_pathogenic	0.8096	pathogenic	0.125	Stabilizing	0.999	D	0.706	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.