TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30402	91429;91430;91431	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
N2AB	28761	86506;86507;86508	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
N2A	27834	83725;83726;83727	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
N2B	21337	64234;64235;64236	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
Novex-1	21462	64609;64610;64611	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
Novex-2	21529	64810;64811;64812	chr2:178551696;178551695;178551694	chr2:179416423;179416422;179416421
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Fn3-109
• Domain position: 79
• Structural Position: 111
• Q(SASA): 0.2233
• 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
E/K	None	None	0.984	N	0.488	0.318	0.317084106153	gnomAD-4.0.0	1.59549E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86697E-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
E/A	0.2654	likely_benign	0.2636	benign	-0.697	Destabilizing	0.992	D	0.598	neutral	N	0.479595127	None	None	N
E/C	0.8188	likely_pathogenic	0.8251	pathogenic	-0.583	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
E/D	0.5701	likely_pathogenic	0.5796	pathogenic	-1.47	Destabilizing	0.992	D	0.455	neutral	N	0.483548011	None	None	N
E/F	0.8395	likely_pathogenic	0.8307	pathogenic	-0.912	Destabilizing	1.0	D	0.879	deleterious	None	None	None	None	N
E/G	0.4261	ambiguous	0.4171	ambiguous	-1.041	Destabilizing	0.999	D	0.755	deleterious	N	0.46840627	None	None	N
E/H	0.6814	likely_pathogenic	0.6546	pathogenic	-1.236	Destabilizing	1.0	D	0.712	prob.delet.	None	None	None	None	N
E/I	0.3167	likely_benign	0.3383	benign	0.231	Stabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
E/K	0.2178	likely_benign	0.1968	benign	-0.892	Destabilizing	0.984	D	0.488	neutral	N	0.48028856	None	None	N
E/L	0.4669	ambiguous	0.4656	ambiguous	0.231	Stabilizing	0.998	D	0.841	deleterious	None	None	None	None	N
E/M	0.4272	ambiguous	0.4307	ambiguous	0.758	Stabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
E/N	0.6093	likely_pathogenic	0.6232	pathogenic	-1.182	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	N
E/P	0.9931	likely_pathogenic	0.9933	pathogenic	-0.057	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
E/Q	0.1277	likely_benign	0.1142	benign	-1.006	Destabilizing	0.916	D	0.248	neutral	N	0.463068236	None	None	N
E/R	0.372	ambiguous	0.327	benign	-0.906	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
E/S	0.3788	ambiguous	0.367	ambiguous	-1.604	Destabilizing	0.994	D	0.532	neutral	None	None	None	None	N
E/T	0.3828	ambiguous	0.377	ambiguous	-1.298	Destabilizing	0.999	D	0.763	deleterious	None	None	None	None	N
E/V	0.1859	likely_benign	0.1948	benign	-0.057	Destabilizing	0.999	D	0.831	deleterious	N	0.423522839	None	None	N
E/W	0.9533	likely_pathogenic	0.948	pathogenic	-1.077	Destabilizing	1.0	D	0.858	deleterious	None	None	None	None	N
E/Y	0.8036	likely_pathogenic	0.7961	pathogenic	-0.752	Destabilizing	1.0	D	0.871	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.