TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26600	80023;80024;80025	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
N2AB	24959	75100;75101;75102	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
N2A	24032	72319;72320;72321	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
N2B	17535	52828;52829;52830	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
Novex-1	17660	53203;53204;53205	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
Novex-2	17727	53404;53405;53406	chr2:178566334;178566333;178566332	chr2:179431061;179431060;179431059
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: Ig-138
• Domain position: 7
• Structural Position: 9
• Q(SASA): 0.9698
• 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
K/N	None	None	0.988	D	0.58	0.442	0.393316636838	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
K/A	0.8776	likely_pathogenic	0.8519	pathogenic	0.032	Stabilizing	0.968	D	0.54	neutral	None	None	None	None	I
K/C	0.9458	likely_pathogenic	0.9384	pathogenic	-0.244	Destabilizing	1.0	D	0.658	neutral	None	None	None	None	I
K/D	0.9388	likely_pathogenic	0.931	pathogenic	0.098	Stabilizing	0.991	D	0.541	neutral	None	None	None	None	I
K/E	0.7816	likely_pathogenic	0.7162	pathogenic	0.087	Stabilizing	0.919	D	0.499	neutral	D	0.535907848	None	None	I
K/F	0.9851	likely_pathogenic	0.9822	pathogenic	-0.298	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
K/G	0.8877	likely_pathogenic	0.8702	pathogenic	-0.121	Destabilizing	0.991	D	0.477	neutral	None	None	None	None	I
K/H	0.7167	likely_pathogenic	0.6867	pathogenic	-0.364	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	I
K/I	0.9198	likely_pathogenic	0.9036	pathogenic	0.349	Stabilizing	0.994	D	0.651	neutral	D	0.531592666	None	None	I
K/L	0.8481	likely_pathogenic	0.8194	pathogenic	0.349	Stabilizing	0.991	D	0.477	neutral	None	None	None	None	I
K/M	0.8013	likely_pathogenic	0.7511	pathogenic	0.174	Stabilizing	0.999	D	0.599	neutral	None	None	None	None	I
K/N	0.8972	likely_pathogenic	0.8752	pathogenic	0.245	Stabilizing	0.988	D	0.58	neutral	D	0.536947998	None	None	I
K/P	0.9687	likely_pathogenic	0.9717	pathogenic	0.269	Stabilizing	0.995	D	0.607	neutral	None	None	None	None	I
K/Q	0.4644	ambiguous	0.4097	ambiguous	0.067	Stabilizing	0.414	N	0.325	neutral	N	0.497120174	None	None	I
K/R	0.1167	likely_benign	0.1102	benign	0.025	Stabilizing	0.919	D	0.517	neutral	N	0.491655639	None	None	I
K/S	0.904	likely_pathogenic	0.8829	pathogenic	-0.227	Destabilizing	0.968	D	0.557	neutral	None	None	None	None	I
K/T	0.74	likely_pathogenic	0.6973	pathogenic	-0.103	Destabilizing	0.988	D	0.545	neutral	N	0.492724357	None	None	I
K/V	0.8887	likely_pathogenic	0.8666	pathogenic	0.269	Stabilizing	0.991	D	0.561	neutral	None	None	None	None	I
K/W	0.9605	likely_pathogenic	0.9591	pathogenic	-0.345	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/Y	0.945	likely_pathogenic	0.9368	pathogenic	0.028	Stabilizing	0.998	D	0.594	neutral	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.