TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8983	27172;27173;27174	chr2:178713187;178713186;178713185	chr2:179577914;179577913;179577912
N2AB	8666	26221;26222;26223	chr2:178713187;178713186;178713185	chr2:179577914;179577913;179577912
N2A	7739	23440;23441;23442	chr2:178713187;178713186;178713185	chr2:179577914;179577913;179577912
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-75
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0663
• 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
L/F	rs878969676	-1.569	0.99	D	0.598	0.58	0.510466299808	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
L/F	rs878969676	-1.569	0.99	D	0.598	0.58	0.510466299808	gnomAD-4.0.0	6.84241E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99491E-06	0	0
L/V	rs2154296469	None	0.822	D	0.685	0.414	0.416075642716	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	1.9253E-04	None	0	0	0	0	0
L/V	rs2154296469	None	0.822	D	0.685	0.414	0.416075642716	gnomAD-4.0.0	6.56711E-06	None	None	None	None	N	None	0	0	None	0	1.92976E-04	None	0	0	0	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
L/A	0.9372	likely_pathogenic	0.9533	pathogenic	-2.245	Highly Destabilizing	0.076	N	0.644	neutral	None	None	None	None	N
L/C	0.9173	likely_pathogenic	0.9479	pathogenic	-1.519	Destabilizing	0.998	D	0.759	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9996	pathogenic	-3.121	Highly Destabilizing	0.956	D	0.858	deleterious	None	None	None	None	N
L/E	0.9953	likely_pathogenic	0.9973	pathogenic	-2.795	Highly Destabilizing	0.956	D	0.847	deleterious	None	None	None	None	N
L/F	0.4301	ambiguous	0.501	ambiguous	-1.317	Destabilizing	0.99	D	0.598	neutral	D	0.544575722	None	None	N
L/G	0.9892	likely_pathogenic	0.9926	pathogenic	-2.851	Highly Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
L/H	0.9831	likely_pathogenic	0.9908	pathogenic	-2.801	Highly Destabilizing	0.994	D	0.87	deleterious	None	None	None	None	N
L/I	0.2688	likely_benign	0.3407	ambiguous	-0.424	Destabilizing	0.904	D	0.673	neutral	D	0.535167973	None	None	N
L/K	0.9904	likely_pathogenic	0.9943	pathogenic	-1.572	Destabilizing	0.754	D	0.833	deleterious	None	None	None	None	N
L/M	0.2633	likely_benign	0.3058	benign	-0.713	Destabilizing	0.993	D	0.633	neutral	None	None	None	None	N
L/N	0.9955	likely_pathogenic	0.9972	pathogenic	-2.321	Highly Destabilizing	0.956	D	0.859	deleterious	None	None	None	None	N
L/P	0.9973	likely_pathogenic	0.9984	pathogenic	-1.022	Destabilizing	0.978	D	0.863	deleterious	None	None	None	None	N
L/Q	0.9742	likely_pathogenic	0.9849	pathogenic	-1.927	Destabilizing	0.956	D	0.841	deleterious	None	None	None	None	N
L/R	0.9777	likely_pathogenic	0.9874	pathogenic	-1.836	Destabilizing	0.043	N	0.733	prob.delet.	None	None	None	None	N
L/S	0.9894	likely_pathogenic	0.9938	pathogenic	-2.806	Highly Destabilizing	0.89	D	0.831	deleterious	D	0.582812148	None	None	N
L/T	0.9761	likely_pathogenic	0.9851	pathogenic	-2.311	Highly Destabilizing	0.86	D	0.778	deleterious	None	None	None	None	N
L/V	0.2897	likely_benign	0.3565	ambiguous	-1.022	Destabilizing	0.822	D	0.685	prob.neutral	D	0.546804221	None	None	N
L/W	0.9258	likely_pathogenic	0.9567	pathogenic	-1.774	Destabilizing	0.998	D	0.831	deleterious	None	None	None	None	N
L/Y	0.9425	likely_pathogenic	0.9613	pathogenic	-1.5	Destabilizing	0.993	D	0.753	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.