TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15852	47779;47780;47781	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
N2AB	14211	42856;42857;42858	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
N2A	13284	40075;40076;40077	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
N2B	6787	20584;20585;20586	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
Novex-1	6912	20959;20960;20961	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
Novex-2	6979	21160;21161;21162	chr2:178617797;178617796;178617795	chr2:179482524;179482523;179482522
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: Fn3-2
• Domain position: 95
• Structural Position: 129
• Q(SASA): 0.3667
• 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	0.999	N	0.762	0.413	0.228597637076	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	0.3735	ambiguous	0.4078	ambiguous	-0.116	Destabilizing	0.998	D	0.811	deleterious	None	None	None	None	N
K/C	0.7036	likely_pathogenic	0.7038	pathogenic	-0.397	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/D	0.737	likely_pathogenic	0.7671	pathogenic	0.249	Stabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
K/E	0.2511	likely_benign	0.2834	benign	0.294	Stabilizing	0.997	D	0.827	deleterious	N	0.466745968	None	None	N
K/F	0.7495	likely_pathogenic	0.7796	pathogenic	-0.117	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
K/G	0.6587	likely_pathogenic	0.6873	pathogenic	-0.376	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/H	0.3509	ambiguous	0.3413	ambiguous	-0.561	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/I	0.2949	likely_benign	0.3404	ambiguous	0.505	Stabilizing	0.999	D	0.803	deleterious	N	0.465400562	None	None	N
K/L	0.3329	likely_benign	0.3688	ambiguous	0.505	Stabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	N
K/M	0.203	likely_benign	0.2256	benign	0.225	Stabilizing	1.0	D	0.706	prob.delet.	None	None	None	None	N
K/N	0.4663	ambiguous	0.526	ambiguous	0.031	Stabilizing	0.999	D	0.724	deleterious	N	0.470499325	None	None	N
K/P	0.6886	likely_pathogenic	0.7056	pathogenic	0.328	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
K/Q	0.1578	likely_benign	0.1624	benign	-0.104	Destabilizing	0.999	D	0.743	deleterious	N	0.472649412	None	None	N
K/R	0.0882	likely_benign	0.088	benign	-0.108	Destabilizing	0.997	D	0.773	deleterious	N	0.460117684	None	None	N
K/S	0.4849	ambiguous	0.5219	ambiguous	-0.568	Destabilizing	0.998	D	0.768	deleterious	None	None	None	None	N
K/T	0.1503	likely_benign	0.1622	benign	-0.348	Destabilizing	0.999	D	0.762	deleterious	N	0.437649184	None	None	N
K/V	0.2585	likely_benign	0.2862	benign	0.328	Stabilizing	0.999	D	0.778	deleterious	None	None	None	None	N
K/W	0.8014	likely_pathogenic	0.7812	pathogenic	-0.059	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
K/Y	0.6656	likely_pathogenic	0.6804	pathogenic	0.271	Stabilizing	1.0	D	0.794	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.