TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14352	43279;43280;43281	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
N2AB	12711	38356;38357;38358	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
N2A	11784	35575;35576;35577	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
N2B	5287	16084;16085;16086	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
Novex-1	5412	16459;16460;16461	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
Novex-2	5479	16660;16661;16662	chr2:178633219;178633218;178633217	chr2:179497946;179497945;179497944
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-94
• Domain position: 34
• Structural Position: 49
• Q(SASA): 0.2702
• 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/Q	rs561547028	-1.051	0.931	N	0.633	0.304	0.0986583533028	gnomAD-2.1.1	8.07E-06	None	None	None	None	I	None	1.29299E-04	0	None	0	0	None	0	None	0	0	0
K/Q	rs561547028	-1.051	0.931	N	0.633	0.304	0.0986583533028	1000 genomes	3.99361E-04	None	None	None	None	I	None	1.5E-03	0	None	None	0	0	None	None	None	0	None
K/Q	rs561547028	-1.051	0.931	N	0.633	0.304	0.0986583533028	gnomAD-4.0.0	2.47975E-06	None	None	None	None	I	None	5.33262E-05	0	None	0	0	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
K/A	0.6286	likely_pathogenic	0.5711	pathogenic	-0.882	Destabilizing	0.835	D	0.581	neutral	None	None	None	None	I
K/C	0.7839	likely_pathogenic	0.7638	pathogenic	-1.196	Destabilizing	0.998	D	0.754	deleterious	None	None	None	None	I
K/D	0.8602	likely_pathogenic	0.8331	pathogenic	-0.788	Destabilizing	0.973	D	0.688	prob.delet.	None	None	None	None	I
K/E	0.3716	ambiguous	0.3325	benign	-0.641	Destabilizing	0.792	D	0.533	neutral	N	0.424638224	None	None	I
K/F	0.6271	likely_pathogenic	0.595	pathogenic	-0.578	Destabilizing	0.998	D	0.742	deleterious	None	None	None	None	I
K/G	0.785	likely_pathogenic	0.7334	pathogenic	-1.269	Destabilizing	0.835	D	0.673	prob.neutral	None	None	None	None	I
K/H	0.3235	likely_benign	0.3013	benign	-1.586	Destabilizing	0.998	D	0.649	prob.neutral	None	None	None	None	I
K/I	0.2511	likely_benign	0.247	benign	0.141	Stabilizing	0.973	D	0.774	deleterious	None	None	None	None	I
K/L	0.3024	likely_benign	0.2834	benign	0.141	Stabilizing	0.947	D	0.693	prob.delet.	None	None	None	None	I
K/M	0.1436	likely_benign	0.1409	benign	-0.003	Destabilizing	0.997	D	0.636	neutral	N	0.43295102	None	None	I
K/N	0.5385	ambiguous	0.4966	ambiguous	-0.999	Destabilizing	0.964	D	0.639	neutral	D	0.533617518	None	None	I
K/P	0.991	likely_pathogenic	0.988	pathogenic	-0.172	Destabilizing	0.016	N	0.401	neutral	None	None	None	None	I
K/Q	0.1741	likely_benign	0.1658	benign	-1.065	Destabilizing	0.931	D	0.633	neutral	N	0.425186063	None	None	I
K/R	0.1047	likely_benign	0.0981	benign	-0.834	Destabilizing	0.027	N	0.333	neutral	N	0.492361148	None	None	I
K/S	0.6059	likely_pathogenic	0.5505	ambiguous	-1.666	Destabilizing	0.835	D	0.599	neutral	None	None	None	None	I
K/T	0.2402	likely_benign	0.2114	benign	-1.3	Destabilizing	0.931	D	0.709	prob.delet.	N	0.431018346	None	None	I
K/V	0.3125	likely_benign	0.2999	benign	-0.172	Destabilizing	0.973	D	0.65	prob.neutral	None	None	None	None	I
K/W	0.7348	likely_pathogenic	0.7138	pathogenic	-0.462	Destabilizing	0.998	D	0.677	prob.neutral	None	None	None	None	I
K/Y	0.4795	ambiguous	0.4568	ambiguous	-0.111	Destabilizing	0.991	D	0.725	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.