TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2206	6841;6842;6843	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
N2AB	2206	6841;6842;6843	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
N2A	2206	6841;6842;6843	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
N2B	2160	6703;6704;6705	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
Novex-1	2160	6703;6704;6705	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
Novex-2	2160	6703;6704;6705	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820
Novex-3	2206	6841;6842;6843	chr2:178775095;178775094;178775093	chr2:179639822;179639821;179639820

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-11
• Domain position: 33
• Structural Position: 47
• Q(SASA): 0.3576
• 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/R	None	None	0.999	N	0.587	0.428	0.339316883193	gnomAD-4.0.0	1.59074E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85678E-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	0.358	ambiguous	0.347	ambiguous	-0.854	Destabilizing	0.999	D	0.698	prob.neutral	None	None	None	None	N
K/C	0.6109	likely_pathogenic	0.5896	pathogenic	-0.801	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/D	0.7594	likely_pathogenic	0.7558	pathogenic	-0.768	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
K/E	0.2518	likely_benign	0.2478	benign	-0.556	Destabilizing	0.999	D	0.607	neutral	N	0.506384919	None	None	N
K/F	0.7469	likely_pathogenic	0.7289	pathogenic	-0.078	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
K/G	0.5896	likely_pathogenic	0.572	pathogenic	-1.311	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/H	0.2743	likely_benign	0.2645	benign	-1.466	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
K/I	0.2898	likely_benign	0.2792	benign	0.392	Stabilizing	1.0	D	0.845	deleterious	D	0.533736486	None	None	N
K/L	0.3088	likely_benign	0.2912	benign	0.392	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
K/M	0.2054	likely_benign	0.1952	benign	0.092	Stabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
K/N	0.4627	ambiguous	0.4636	ambiguous	-1.122	Destabilizing	1.0	D	0.743	deleterious	D	0.592938095	None	None	N
K/P	0.9818	likely_pathogenic	0.9797	pathogenic	0.004	Stabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
K/Q	0.1263	likely_benign	0.1217	benign	-0.934	Destabilizing	1.0	D	0.737	prob.delet.	N	0.509454536	None	None	N
K/R	0.0916	likely_benign	0.0881	benign	-0.956	Destabilizing	0.999	D	0.587	neutral	N	0.498357913	None	None	N
K/S	0.4003	ambiguous	0.3915	ambiguous	-1.674	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
K/T	0.1467	likely_benign	0.1421	benign	-1.231	Destabilizing	1.0	D	0.77	deleterious	N	0.482561214	None	None	N
K/V	0.2828	likely_benign	0.2679	benign	0.004	Stabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
K/W	0.7906	likely_pathogenic	0.7717	pathogenic	-0.07	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
K/Y	0.6586	likely_pathogenic	0.641	pathogenic	0.209	Stabilizing	1.0	D	0.802	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.