TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25289	76090;76091;76092	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
N2AB	23648	71167;71168;71169	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
N2A	22721	68386;68387;68388	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
N2B	16224	48895;48896;48897	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
Novex-1	16349	49270;49271;49272	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
Novex-2	16416	49471;49472;49473	chr2:178570267;178570266;178570265	chr2:179434994;179434993;179434992
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: Fn3-71
• Domain position: 86
• Structural Position: 119
• Q(SASA): 0.5037
• Predicted PPI site: I

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/G	None	None	0.988	N	0.675	0.352	0.367425347029	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
E/A	0.3258	likely_benign	0.285	benign	-0.513	Destabilizing	0.958	D	0.652	neutral	N	0.478775071	None	None	I
E/C	0.9181	likely_pathogenic	0.9124	pathogenic	-0.195	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
E/D	0.1855	likely_benign	0.1535	benign	-0.526	Destabilizing	0.979	D	0.557	neutral	N	0.496759522	None	None	I
E/F	0.8548	likely_pathogenic	0.8377	pathogenic	-0.354	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
E/G	0.4365	ambiguous	0.3806	ambiguous	-0.729	Destabilizing	0.988	D	0.675	prob.neutral	N	0.490776486	None	None	I
E/H	0.7395	likely_pathogenic	0.719	pathogenic	-0.141	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
E/I	0.4785	ambiguous	0.4443	ambiguous	0.03	Stabilizing	0.995	D	0.755	deleterious	None	None	None	None	I
E/K	0.3287	likely_benign	0.3188	benign	0.054	Stabilizing	0.958	D	0.625	neutral	N	0.468166007	None	None	I
E/L	0.5626	ambiguous	0.5319	ambiguous	0.03	Stabilizing	0.991	D	0.729	prob.delet.	None	None	None	None	I
E/M	0.5942	likely_pathogenic	0.5648	pathogenic	0.13	Stabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	I
E/N	0.4408	ambiguous	0.3904	ambiguous	-0.235	Destabilizing	0.995	D	0.715	prob.delet.	None	None	None	None	I
E/P	0.6066	likely_pathogenic	0.6084	pathogenic	-0.131	Destabilizing	0.086	N	0.471	neutral	None	None	None	None	I
E/Q	0.2644	likely_benign	0.2505	benign	-0.207	Destabilizing	0.994	D	0.693	prob.neutral	N	0.481497322	None	None	I
E/R	0.5249	ambiguous	0.5189	ambiguous	0.339	Stabilizing	0.995	D	0.713	prob.delet.	None	None	None	None	I
E/S	0.3964	ambiguous	0.3507	ambiguous	-0.419	Destabilizing	0.968	D	0.679	prob.neutral	None	None	None	None	I
E/T	0.4662	ambiguous	0.425	ambiguous	-0.251	Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	I
E/V	0.3087	likely_benign	0.2822	benign	-0.131	Destabilizing	0.994	D	0.704	prob.neutral	D	0.524850201	None	None	I
E/W	0.9666	likely_pathogenic	0.9629	pathogenic	-0.185	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	I
E/Y	0.7726	likely_pathogenic	0.7594	pathogenic	-0.115	Destabilizing	0.998	D	0.75	deleterious	None	None	None	None	I

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.